Circulating miRNA-21 as a diagnostic biomarker for acute coronary syndrome: a systematic review and meta-analysis of diagnostic test accuracy study.

Background: Both early detection and treatment for acute coronary syndrome (ACS) have positively affected prognosis. A microRNA, miRNA-21 (miR-21), may have additional diagnostic potential for ACS among the others. This systematic review and meta-analysis aimed to evaluate the potential role of miR-21 in identifying ACS. Methods: PubMed, EMBASE and CENTRAL databases were searched up to March 17, 2024, for case-control and cohort studies assessing the diagnostic value of circulating miR-21 in patients with ACS. The search was limited to studies published in either English or Chinese. The primary outcome was the discriminative ability to circulate miR-21 for ACS, represented by the area under the standard receiver operating characteristic curve (AUC) analysis. Meta-analyses combined the AUCs using a random-effects model. Heterogeneity among the studies was detected by the I2 and Q statistics. The quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Publication bias analysis was assessed constructing by the Egger's test (PROSPERO: CRD42020209424). Results: Eleven case-control studies containing a total of 2,413 subjects with 1,236 ACS cases and 1,177 controls were included. The mean age of participants in these studies ranges between 51.0 and 69.0 years. The meta-analysis showed an overall pooled AUC of 0.779 [95% confidence interval (CI): 0.715-0.843], with high heterogeneity noted between the studies (Q statistic =190.64, I2=94.23%, P<0.001). In subgroup analyses according to the subtypes of ACS, a pooled AUC of 0.767 (95% CI: 0.648-0.887) was derived from the studies focused on acute myocardial infarction cases only. The pooled AUC for unstable angina was 0.770 (95% CI: 0.718-0.822). In subgroup analyses according to the types of control groups, pooled AUC for ACS versus healthy controls was 0.779 (95% CI: 0.715-0.843), whereas the pooled AUC for ACS versus unhealthy controls was 0.740 (95% CI: 0.645-0.836). The quality assessment showed that the studies' overall quality was moderate. No evidence of publication bias was noted (P=0.49). Conclusions: Circulating miR-21 shows abilities to differentiate between ACS and non-ACS, suggesting its potential as a novel diagnostic biomarker for ACS. However, the evidence is weakened by high heterogeneity observed among the studies. Further research is essential before it can be applied in clinical practice.

Differentially expressed miR-127, miR-150, and miR-145 in serum extracellular vesicles are novel diagnostic biomarkers of unstable angina.

Background: Specific and sensitive diagnostic biomarkers for unstable angina (UA) are currently scarce. The diagnosis of UA usually relies on medical history and physician experience. This study aimed to analyze the expression profiles of microRNAs (miRNAs) in the serum extracellular vesicles (EVs) of UA patients, thus identifying potential diagnostic biomarkers of UA. Methods: This study is a prospective study and participants were recruited randomly. A total of 142 patients with UA, 8 with non-ST-elevation myocardial infarction (NSTEMI), and 8 with stable angina (SA) at Nanjing Hospital of Traditional Chinese Medicine Affiliated with Nanjing University of Chinese Medicine from January 2019 to February 2022 were recruited. Fifty-eight healthy volunteers (HVs) were recruited to the control group during the same period. Differentially expressed miRNAs in serum exosomes of UA patients were first identified by high-throughput sequencing, followed by verification via quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Our findings aim to explore their diagnostic potentials in UA, and their biological functions, as well as the correlation between conventional biochemical indexes of UA. Results: MiR-127, miR-150, and miR-145 were differentially expressed miRNAs in the serum EVs of 8 UA patients, 8 NSTEMI patients, 8 SA patients, and 8 HVs by high-throughput sequencing, which were downregulated in UA patients versus HVs. Moreover, the relative levels of differentially expressed miRNAs in the serum EVs of the remaining UA patients and HVs were measured by qRT-PCR. The area under the curve of miR-127, miR-150, and miR-145 in distinguishing UA patients from HVs was 0.872, 0.856, and 0.803, respectively. Notably, the area under the curve of the combination of the three differentially expressed miRNAs for diagnosing UA was 0.944. A GO analysis revealed that miR-127, miR-150, and miR-145 were mainly enriched in cell adhesion and migration, whereas KEGG pathway enrichment analysis showed that they were enriched in the PI3K-Akt, MAPK, and Hippo signaling pathways. Multivariable logistic regression analysis identified cardiac troponin I (cTnI) (P=0.0006), miR-127 (P=0.0001), miR-150 (P=0.0004), and miR-145 (P=0.0005) as independent risk factors for UA. Spearman's rank correlation test showed a significant correlation between cTnI and miR-127 (r=0.1988, P=0.0067). Conclusions: MiR-127, miR-150, and miR-145 in serum EVs are closely linked with UA and serve as novel diagnostic biomarkers.

Hypoxia-associated genes predicting future risk of myocardial infarction: a GEO database-based study.

Background: Patients with unstable angina (UA) are prone to myocardial infarction (MI) after an attack, yet the altered molecular expression profile therein remains unclear. The current work aims to identify the characteristic hypoxia-related genes associated with UA/MI and to develop a predictive model of hypoxia-related genes for the progression of UA to MI. Methods and results: Gene expression profiles were obtained from the GEO database. Then, differential expression analysis and the WGCNA method were performed to select characteristic genes related to hypoxia. Subsequently, all 10 hypoxia-related genes were screened using the Lasso regression model and a classification model was established. The area under the ROC curve of 1 shows its excellent classification performance and is confirmed on the validation set. In parallel, we construct a nomogram based on these genes, showing the risk of MI in patients with UA. Patients with UA and MI had their immunological status determined using CIBERSORT. These 10 genes were primarily linked to B cells and some inflammatory cells, according to correlation analysis. Conclusion: Overall, GWAS identified that the CSTF2F UA/MI risk gene promotes atherosclerosis, which provides the basis for the design of innovative cardiovascular drugs by targeting CSTF2F.

Efficacy and safety of eight types Salvia miltiorrhiza injections in the treatment of unstable angina pectoris: A network meta-analysis.

Background: Salvia miltiorrhiza Bunge. [Lamiaceae, danshen] injection classes (SMIC) is widely used in the treatment of unstable angina (UA). However, it is uncertain which SMIC is more effective in terms of UA efficacy. The purpose of this Network Meta-analysis (NMA) was to compare the treatment effects of various SMIC to determine the best SMIC for the treatment of UA. Methods: The China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, and Cochrane Library databases were searched to screen randomized controlled trials (RCTs) of SMIC for UA. The search time frame was all from the establishment of the database to May 2022. RevMan 5.3 and Stata 14.0 software were used for NMA. Results: A total of 148 studies including 14,979 patients, including 7,584 cases in the experimental group and 7,395 cases in the control group were included, and eight SMIC were extracted, namely:Danshen injection, Fufang Danshen injection, Guanxinning injection, Danshenchuanxiongqin injection, Danhong injection, Danshentong IIA Huangsuanna injection, Shenxiong Putaotang injection, and Danshenduofensuanyan injection. The results of NMA showed that, in terms of total effective rate, Shenxiong Putaotang injection and Danshenchuanxiongqin injection have the advantage; In terms of ECG efficiency, Danshentong IIA Huangsuanna injection and Danshen injection have an advantage; Danshenchuanxiongqin injection and Danshenduofensuanyan injection were more effective than other SMIC in improving angina pectoris attacks; Shenxiong Putaotang injection has an advantage in improving hs-CRP; Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection have advantages in improving TC and TG, respectively. Conclusion: The eight SMIC included in the current study were effective in treating UA, Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection were both superior in improving all outcome indicators. However, there is still a need for larger samples and high-quality randomized controlled trials for more refined comparisons of various SMIC. Systematic Review Registration: [PROSPERO], identifier [CRD42022350872].

Prevalence, Predictors, and Clinical Presentation of Acute Pericardial Effusion Following Percutaneous Coronary Intervention.

Background: Iatrogenic pericardial effusion (PE) has been demonstrated to lead to cardiac injury as a sign of systemic inflammatory response. Objectives: This study sought to determine the anatomical characteristics and clinical presentation associated with PE after percutaneous coronary intervention (PCI) by using echocardiography. Methods: The clinical outcomes of all patients with coronary artery disease who underwent PCI from July 2014 to December 2018 were evaluated. The quantitative and qualitative analyses of PE were performed. The associations between the presence of PE and procedural factors were also evaluated. Results: A total of 882 patients were enrolled. PE was found in 144 patients (16.3%) and was mostly located in the anterior pericardium at low amounts. The serum levels of high-sensitive C-reaction protein before PCI and troponin T in the group with PE after PCI were significantly higher than those in the group without PE (p < 0.0001). The presence of PE was associated with the procedural time (OR = 1.02, p = 0.035) and the degree of interventional complexity (multiple vessels OR = 1.89, p = 0.014; chronic total occlusion OR = 2.04, p = 0.005; and PCI with rotational atherectomy OR = 1.15, p = 0.011) independent of the number of culprit vessels and stents. During 1-year follow-up, a significantly higher number of cardiac deaths (3) and myocardial infarctions (8) occurred in patients with PE than in patients without PE (P < 0.05). Conclusion: Post-PCI acute PE was frequent, generally mild, mainly asymptomatic, and independently associated with procedural time and complexity. This effusion, which is considered as a cardiac damage marker, could be a predominant clinical sign for long-term prognosis.

A comparison of fractional flow reserve determination and coronary angiography results in patients with unstable angina and analysis of related factors.

BACKGROUND: Coronary angiography (CAG) and fractional flow reserve (FFR) are currently used to identify the lesions and guide the treatment of unstable angina (UA) patients. This study aims to compare the two methods and investigate factors affecting FFR value. METHODS: A total of 284 UA patients (296 coronary artery lesions) were enrolled from the Emergency Department of Anzhen Hospital Affiliated to Capital Medical University from January 2017 to December 2017. CAG and FFR determination were performed in all patients, and the roles of these two methods in guiding the treatment of UA were compared and analyzed. The subjects were divided into FFR ≤0.8 group and FFR >0.8 group. The general data and laboratory findings were compared between these two groups, and the possible influential factors were analyzed. The statistical analysis of t-test or chi square test was done with SPSS 20.0 software. RESULTS: Of 296 UA lesions, 160 (54.1%) had ≥75% angiographic stenosis and 136 (45.9%) had <75% angiographic stenosis; 168 (56.8%) had an FFR value of ≤0.8 and 128 (43.2%) had an FFR value >0.8. There was no significant difference between these two examination methods (P=0.508, χ2=0.438). Further analysis showed that 43 (26.9%) of the 160 lesions with ≥75% stenosis had an FFR value of >0.8 and did not require PCI; 49 (38.3%) of the 128 lesions with 50-70% stenosis had an FFR value of ≤0.8 and needed PCI; 2 of 8 patients with <50% stenosis had an FFR value of ≤0.8 and needed PCI. If FFR was used as the "gold standard" of PCI, the sensitivity, specificity, positive predictive value, and negative predictive value of CAG in guiding PCI for UA were 69.6%, 66.4%, 73.1%, and 62.5%, respectively. Multivariate analysis with Logistic regression revealed low high-density lipoprotein (HDL) and hypertension were independent risk factors of FFR <0.8 in UA patients. CONCLUSIONS: CAG and FFR readings could be different. A combination of CAG and FFR may help to achieve more accurate and tailored treatment of UA. The history of hypertension is an independent risk factor for FFR in UA patients, and HDL is an independent protective factor.

The clinics of acute coronary syndrome.

Risk stratification and management of patients with chest pain continues to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The throutful evaluation necessitates that the physicians have a high index of suspicion for acute coronary syndrome (ACS) and always keep in mind the myriad of often subtle and atypical presentations of ischemic heart disease, especially in certain patient populations such as the elderly ones. In this article we aim to review and discuss the available evidence on the value of clinical presentation in patients with a suspected ACS, with special emphasis on history, characteristics of chest pain, associated symptoms, atypical presentations, precipitating and relieving factors, drugs, clinical rules and significance of clinical Gestalt.

[Acupuncture combined with medication for blood-stasis in unstable angina patients with different thrombolysis in myocardial infarction risk stratification].

OBJECTIVE: To observe the intervention effects of acupuncture combined with standardized treatment of western medicine on blood-stasis syndrome in unstable angina (UA) patients with different thrombolysis in myo-cardial infarction (TIMI) risk stratification. METHODS: According to TIMI risk score, a total of 72 UA patients were included, 24 cases in low-risk (0 to 2 points) group, 24 cases in moderate-risk (3 to 4 points) group and 24 cases in high-risk (5 to 7 points) group. Based on routine standardized treatment of western medicine, acupuncture was applied at Xinshu (BL 15), Xuehai (SP 10), Geshu (BL 17), Danzhong (CV 17), Jueyinshu (BL 14), Ximen (PC 4) and Neiguan (PC 6) in three groups. Acupuncture was given once a day, 14 days as a session. After one session, each symptom score and total score of blood stasis syndrome were observed. RESULTS: One patient dropped out respectively, and 23 patients in each group were included in the analysis. After treatment, the score of angina symptom and total score of blood stasis syndrome were significantly improved in three groups (all P<0.01). The improvements of each score and total score of blood stasis syndrome in the high-risk group were superior to those in the low-risk group and moderate-risk group (P<0.05, P<0.01). CONCLUSIONS: With the higher TIMI scores, the blood stasis syndrome is aggravated accordingly. Acupuncture combined with standardized treatment of western medicine could effectively intervene blood stasis syndrome, especially for the score of blood stasis syndrome of patients in high-risk group.