Identification of plaque ruptures using a novel discriminative model comprising biomarkers in patients with acute coronary syndrome.
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ABSTRACT:
SUBMITTER: Kook H
PROVIDER: S-EPMC7677551 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Identification of plaque ruptures using a novel discriminative model comprising biomarkers in patients with acute coronary syndrome.
Kook Hyungdon H Jang Duck Hyun DH Kim Jong-Ho JH Cho Jae-Young JY Joo Hyung Joon HJ Cho Sang-A SA Park Jae Hyoung JH Hong Soon Jun SJ Yu Cheol Woong CW Lim Do-Sun DS
Scientific reports 20201119 1
Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-9 (MMP-9) are inflammatory biomarkers involved in plaque destabilization resulting in acute coronary syndrome (ACS). This study aimed to investigate the diagnostic value of a combination of biomarkers to discriminate plaque ruptures in the setting of ACS. Eighty-five ACS patients with optical coherence tomography (OCT) images of the culprit pla ...[more]
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Project description:Acute coronary syndrome (ACS), consisting of acute myocardial infarction and unstable angina, is the most dangerous and fatal form of coronary heart disease. Acute coronary syndrome has sudden onset and rapid development, which may lead to malignant life-threatening conditions at any time. Therefore, early detection and diagnosis are critical for patients with ACS. Recent studies have found that noncoding RNA is of great significance in the diagnosis and treatment of cardiovascular diseases. In this review, we summarized recent data on circulating noncoding RNAs (including microRNA, long noncoding RNA, and circular RNA) as diagnostic and prognostic markers in ACS including acute myocardial infarction and unstable angina. Specifically, microRNAs (miRNAs) as diagnostic markers are divided into three types: miRNAs of increased expression in ACS, miRNAs of decreased expression in ACS, and miRNAs of contradictory expression in ACS. Moreover, we described these miRNAs of increased expression in ACS based on miRNAs family. This review may result in a great guidance of noncoding RNAs as biomarkers for ACS in clinical practice.
| S-EPMC7154975 | biostudies-literature
Project description:AIM:Acute coronary syndrome (ACS), a leading cause of morbidity and mortality worldwide, is among the most serious cardiovascular diseases. Circadian rhythms are present in almost all organisms. In clinical practice, we have found that ACS is closely related to these circadian rhythms. However, the relationship between circadian rhythms and plaque instability in ACS patients is incompletely understood. The aim of this study is to provide new insights into the relationship between circadian rhythms and plaque instability in ACS patients. METHODS:We enrolled patients with ACS and individuals with normal coronary artery function in this study. The Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire (IPAQ) and Healthy Diet Score (HDS) were used to evaluate circadian rhythms. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the mRNA expression levels of muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), Cryptochrome1 (Cry1), Period2 (Per2), nuclear receptor subfamily 1, group D, member 1 (Rev-erb?), and matrix metalloproteinases MMP2 and MMP9. RESULTS:AIS scores and PSQI scores were significantly higher in patients with ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA) than in the normal controls (NCs) (P < 0.05). The IPAQ scores of the NCs and patients with UA were significantly higher than in patients with STEMI and NSTEMI (P < 0.05). Notably higher HDS scores were recorded for the NCs compared to those of patients with UA, NSTEMI, and STEMI (P < 0.05). Consistent with these findings, compared with the NCs, the lowest levels of Bmal1, Clock, Cry1, Per2 and Rev-erb? mRNAs were detected in patients with STEMI, followed by patients with NSTEMI and then patients with UA (P < 0.05). Furthermore, the levels of MMP2 and MMP9 mRNA were significantly higher in the patients with STEMI, NSTEMI, and UA than those in the NCs (P < 0.05). In addition, we found that the levels of MMP mRNA negatively correlated with the levels of clock genes mRNAs (P < 0.05, respectively). CONCLUSIONS:Based on our data, the circadian rhythms and clock genes are correlatively with the occurrence of ACS, and the expression levels of clock genes are negatively correlated with plaque stability in ACS patients.
| S-EPMC6949736 | biostudies-literature
Project description:BackgroundAcute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored regulatory mechanism of miR-335-5p on macrophage innate immune response, atherosclerotic vulnerable plaque formation, and revascularization in ACS in relation to Notch signaling.MethodsACS-related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, or inhibitor of Notch signaling treatment, IL-6, IL-1?, TNF-?, MCP-1, ICAM-1, and VCAM-1 levels were tested in ACS mice. Additionally, Notch signaling-related genes and matrix metalloproteinases (MMPs) were measured after miR-335-5p interference. Finally, mouse atherosclerosis, lipid accumulation, and the collagen/vessel area ratio of plaque were determined.ResultsmiR-335-5p targeted JAG1 and mediated Notch signaling in ACS. miR-335-5p up-regulation and Notch signaling inhibition reduced expression of JAG1, Notch pathway-related genes, IL-6, IL-1?, TNF-?, MCP-1, ICAM-1, VCAM-1, and MMPs, but promote TIMP1 and TIMP2 expression. Additionally, vulnerable plaques were decreased and collagen fiber contents were observed to increase after miR-335-5p overexpression and Notch signaling inhibition.ConclusionsOverexpression of miR-335-5p inhibited innate immune response of macrophage, reduced atherosclerotic vulnerable plaque formation, and promoted revascularization in ACS mice targeting JAG1 through Notch signaling.
| S-EPMC7891542 | biostudies-literature
Project description:ImportancePlaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known.ObjectiveTo ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS.Design, setting, and participantsThis multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019.ExposuresWhole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque).Main outcomes and measuresAssociation between calcium density and future ACS risk.ResultsA total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases.Conclusions and relevanceResults of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.
| S-EPMC6990946 | biostudies-literature
Project description:Coronary plaque rupture is the most common cause of acute coronary syndrome. However, the timely biomarker-based diagnosis of plaque rupture remains a major unmet clinical challenge. Balloon dilatation and stent implantation during percutaneous coronary intervention (PCI) could cause plaque injury and rupture. Here we aimed to assess the possibility of circulating microRNAs (miRNAs) as biomarkers of acute coronary plaque rupture by virtue of the natural model of PCI-induced plaque rupture. Stable coronary artery disease patients underwent PCI with single stent implantation were recruited and a three-phase approach was conducted in the present study: (i) profiling of plasma miRNAs in a group of patients before (0 h) and after balloon dilatation for 1 h (1 h vs. 0 h), (ii) replication of significant miRNAs in the second group of patients (1 h vs. 0 h), (iii) validation of a multi-miRNAs panel in the third group of patients (0.5 h, 1 h vs. 0 h). Out of 24 miRNAs selected for replication, 6 miRNAs remained significantly associated with plaque rupture. In the validation phase, combinations of miR-483-5p and miR-451a showed the highest area under the receiver-operating-characteristic curve (AUC) (0.982; CI: 0.907-0.999) in patients with plaque rupture for 0.5 h; combinations of miR-483-5p and miR-155-5p showed the highest AUC (0.898; CI: 0.790-0.962) after plaque rupture for 1 h. In conclusion, using a profiling-replication-validation model, we identified 3 miRNAs including miR-155-5p, miR-483-5p and miR-451a, which may be biomarkers for the early identification of plaque rupture.
| S-EPMC5564633 | biostudies-other
Project description:Background High-risk plaque (HRP) features as detected by coronary computed tomography angiography (CTA) predict acute coronary syndrome (ACS). We sought to determine whether coronary CTA-specific definitions of HRP improve discrimination of patients with ACS as compared with definitions from intravascular ultrasound (IVUS). Methods and Results In patients with suspected ACS, randomized to coronary CTA in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II) trial, we retrospectively performed semiautomated quantitative analysis of HRP (including remodeling index, plaque burden as derived by plaque area, low computed tomography attenuation plaque volume) and degree of luminal stenosis and analyzed the performance of traditional IVUS thresholds to detect ACS. Furthermore, we derived CTA-specific thresholds in patients with ACS to detect culprit lesions and applied those to all patients to calculate the discriminatory ability to detect ACS in comparison to IVUS thresholds. Of 472 patients, 255 patients (56±7.8 years; 63% men) had coronary plaque. In 32 patients (6.8%) with ACS, culprit plaques (n=35) differed from nonculprit plaques (n=172) with significantly greater values for all HRP features except minimal luminal area (significantly lower; all P<0.01). IVUS definitions showed good performance while minimal luminal area (odds ratio: 6.82; P=0.014) and plaque burden (odds ratio: 5.71; P=0.008) were independently associated with ACS but not remodeling index (odds ratio: 0.78; P=0.673). Optimized CTA-specific thresholds for plaque burden (area under the curve: 0.832 versus 0.676) and degree of stenosis (area under the curve: 0.826 versus 0.721) showed significantly higher diagnostic performance for ACS as compared with IVUS-based thresholds (all P<0.05) with borderline significance for minimal luminal area (area under the curve: 0.817 versus 0.742; P=0.066). Conclusions CTA-specific definitions of HRP features may improve the discrimination of patients with ACS as compared with IVUS-based definitions. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT01084239.
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Project description:ImportancePatients with culprit plaque rupture are known to have pancoronary plaque vulnerability. However, the characteristics of nonculprit plaques in patients with acute coronary syndromes caused by plaque erosion are unknown.ObjectiveTo investigate the nonculprit plaque phenotype in patients with acute coronary syndrome according to culprit plaque pathology (erosion vs rupture) by 3-vessel optical coherence tomography imaging.Design, setting, and participantsIn this observational cohort study, between August 2010 and May 2014, 82 patients with acute coronary syndrome who underwent preintervention optical coherence tomography imaging of all 3 major epicardial coronary arteries were enrolled at the Massachusetts General Hospital Optical Coherence Tomography Registry database. Analysis of the data was conducted between November 2016 and July 2017. Patients were classified into 2 groups based on the culprit lesion pathology: 17 patients with culprit plaque erosion and 34 patients with culprit plaque rupture. Thirty-one patients with the absence of culprit rupture or erosion were excluded from further analysis.ExposuresPreintervention 3-vessel optical coherence tomography imaging.Main outcomes and measuresPlaque characteristics at the culprit and nonculprit lesions evaluated by optical coherence tomography.ResultsIn 51 patients (37 men; mean age, 58.7 years), the characteristics of 51 culprit plaques and 216 nonculprit plaques were analyzed. In patients with culprit erosion, the mean (SD) number of nonculprit plaques per patient was smaller (3.4 [1.9] in erosion vs 4.7 [2.1] in rupture, P = .05). Patient-based analysis showed that none of 17 patients with culprit plaque erosion had nonculprit plaque rupture, whereas 26% of the patients (9 of 34) with culprit plaque rupture had nonculprit plaque rupture (P = .02). Plaque-based analysis showed that, compared with the culprit rupture group (n = 158), the culprit erosion group (n = 58) had lower prevalence of plaque rupture (0% vs 8%; P < .001), macrophage accumulation (29% vs 53%; P = .01), microvessels (21% vs 42%; P = .003), and spotty calcium (5% vs 22%; P = .006) in the nonculprit lesions. The prevalence of lipid-rich plaque, thin-cap fibroatheroma, and thrombus did not differ between the groups.Conclusions and relevanceCompared with those with culprit plaque rupture, patients with acute coronary syndrome caused by culprit plaque erosion had a smaller number of nonculprit plaques and the lower levels of panvascular instability, affirming that distinct pathophysiologic mechanisms operate in plaque erosion and plaque rupture.
| S-EPMC5885886 | biostudies-literature
Project description:The paramedics brought a 60-year-old man to the emergency department after a sudden onset of shortness of breath with a subsequent drop in the Glasgow Coma Scale (GCS). On arrival the patient looked peri-arrest. His O2 saturations were 84% on 15?L of oxygen. He had gasping breathing with a completely silent chest and the GCS was 6/15 (E=1, V=1, M=4). The blood gas revealed type-2 respiratory failure. The chest X-ray was unremarkable and ECG was not indicative for cardiac catheterisation lab activation. Bedside shock scan was done which showed global hypokinesia of the left ventricle. In spite of unconvincing ECG and chest X-ray, an acute cardiac event was diagnosed in view of an abnormal bedside echo. The patient was transferred to the cardiac catheterisation lab for urgent percutaneous coronary intervention which revealed critical stenosis of the left main stem coronary artery, which was successfully stented. The patient had a good recovery from the life-threatening event.
| S-EPMC4054466 | biostudies-other
Project description:Background Although most coronary thromboses occur on the surface of lipid-rich plaque ( LRP ) with plaque rupture ( PR ), previous pathological and optical coherence tomography studies demonstrated diversity in the morphological characteristics of culprit plaque underlying the thrombus, including lesions with intact fibrous cap ( IFC ). We investigated the clinical significance of IFC in relation to the presence or absence of LRP observed via optical coherence tomography in culprit lesions of acute coronary syndrome. Methods and Results We investigated 510 patients with acute coronary syndrome who underwent optical coherence tomography for the culprit lesion. Optical coherence tomography analysis included the presence or absence of PR , which were categorized into the PR group and the IFC group, respectively. The IFC group was further categorized on the basis of the presence of LRP . Incidence of major adverse cardiac events ( MACEs ), including cardiac death, myocardial infarction, and clinically driven remote revascularizations, was compared. Culprit lesions were categorized into 328 PR s and 182 IFC s. MACEs occurred in 85 patients (16.7%) during the median follow-up duration of 621 days. LRP was detected in 325 lesions (99%) with PR , whereas 60 (33.0%) of the lesions with IFC did not show LRP . Kaplan-Meier analysis revealed significantly lower MACEs in the IFC group compared with the PR group. Furthermore, the IFC group without LRP showed significantly lower MACEs compared with the IFC group with LRP . Multivariate Cox proportional hazards analysis demonstrated that IFC without LRP was an independent predictor of better prognosis. Conclusions Exclusion of LRP underneath IFC culprit lesions in acute coronary syndrome may predict a lower risk of future MACEs .
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Project description:Psychological constructs are associated with cardiovascular health, but the biological mechanisms mediating these relationships are unknown. We examined relationships between psychological constructs and markers of inflammation, endothelial function, and myocardial strain in a cohort of post-acute coronary syndrome (ACS) patients.Participants (N = 164) attended study visits 2 weeks and 6 months after ACS. During these visits, they completed self-report measures of depressive symptoms, anxiety, optimism, and gratitude; and blood samples were collected for measurement of biomarkers reflecting inflammation, endothelial function, and myocardial strain. Generalized estimating equations and linear regression analyses were performed to examine concurrent and prospective relationships between psychological constructs and biomarkers.In concurrent analyses, depressive symptoms were associated with elevated markers of inflammation (interleukin-17: ? = .047; 95% confidence interval [CI] = .010-.083]), endothelial dysfunction (endothelin-1: ? = .020; 95% [CI] = .004-.037]), and myocardial strain (N-terminal pro-B-type natriuretic peptide: ? = .045; 95% [CI] = .008-.083]), independent of age, sex, medical variables, and anxiety, whereas anxiety was not associated with these markers in multivariable adjusted models. Optimism and gratitude were associated with lower levels of markers of endothelial dysfunction (endothelin-1: gratitude: ? = -.009; 95% [CI] = -.017 to - .001]; optimism: ? = -.009; 95% [CI] = -.016 to - .001]; soluble intercellular adhesion molecule-1: gratitude: ? = -.007; 95% [CI] = -.014 to - .000]), independent of depressive and anxiety symptoms. Psychological constructs at 2 weeks were not prospectively associated with biomarkers at 6 months.Depressive symptoms were associated with more inflammation, myocardial strain, and endothelial dysfunction in the 6 months after ACS, whereas positive psychological constructs were linked to better endothelial function. Larger prospective studies may clarify the directionality of these relationships.Clinicaltrials.gov identifier NCT01709669.
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