Diagnostic value of exercise-induced changes in circulating high sensitive troponin T in stable chest pain patients

Abstract

Objective: We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects.

Methods: CTnT was measured before and 20?h after an exercise test in 157 subjects suspected of coronary artery disease (CAD).

Results: CAD subjects (n?=?41) had higher baseline cTnT levels compared to non-CAD subjects (n?=?116), 6.39?ng/l and 3.00?ng/l, respectively, p?<?0.0001, and were more likely to increase in cTnT (70.7% versus 27.6%, p?<?0.0001). Net Reclassification Index for the combined variable was 19%, p?=?0.02.

Conclusions: Exercise-induced increase in cTnT was found to be associated with CAD and cTnT measurements improved the diagnostic evaluation.     

Increased plasma HB-EGF associated with obesity and coronary artery disease

The mechanism by which the obese subjects are more associated with vascular disease remains unclear. We reported that the adipose tissues produce and secrete many bioactive molecules, conceptualized as adipocytokines. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), produced locally by vascular macrophages and smooth muscle cells, has been suggested to induce the migration and proliferation of vascular smooth muscle cells. The current study reveals that (1) HB-EGF mRNA is abundantly expressed in human adipose tissue, (2) HB-EGF mRNA increases in the fat tissues of obese mice, (3) plasma HB-EGF levels increase in parallel with fat accumulation in human, and (4) the subjects with coronary artery disease have higher plasma HB-EGF levels, associated with fat accumulation. These results suggest that increased plasma HB-EGF derived from the accumulated fat contributes to the higher incidence of vascular disease in obesity, proposing HB-EGF as an adipocytokine directly linking adipovascular axis.     

Oxidative status and reduced glutathione levels in premature coronary artery disease and coronary artery disease

Identifying patients at risk of developing premature coronary artery disease (PCAD) which occurs at age below 45 years old and constitutes approximately 7–10% of coronary artery disease (CAD) worldwide remains a problem. Oxidative stress has been proposed as a crucial step in the early development of PCAD. This study was conducted to determine the oxidative status of PCAD in comparison to CAD patients. PCAD (<45 years old) and CAD (>60 years old) patients were recruited with age-matched controls (n?=?30, each group). DNA damage score, plasma malondialdehyde (MDA) and protein carbonyl content were measured for oxidative damage markers. Antioxidants such as erythrocyte glutathione (GSH), oxidised glutathione (GSSG), and glutathione peroxidase activity (GPx), superoxide dismutase (SOD) and catalase (CAT) were also determined. DNA damage score and protein carbonyl content were significantly higher in both PCAD and CAD when compared to age-matched controls while MDA level was increased only in PCAD (p<.05). In contrast, GSH, GSH/GSSG ratio, α-tocotrienol isomer, and GPx activity were significantly decreased, but only in PCAD when compared to age-matched controls. The decrease in GSH was associated with PCAD (OR?=?0.569 95%CI [0.375???0.864], p?=?.008) and cut-off values of 6.69?μM with areas under the ROC curves (AUROC) 95%CI: 0.88 [0.80–0.96] (sensitivity of 83.3%; specificity of 80%). However, there were no significant differences in SOD and CAT activities in all groups. A higher level of oxidative stress indicated by elevated MDA levels and low levels of GSH, α-tocotrienol and GPx activity in patients below 45 years old may play a role in the development of PCAD and has potential as biomarkers for PCAD.     

PCI及CABG治疗严重病变程度冠心病患者的临床效果比较

目的:比较经皮冠状动脉介入术(Percutaneous Coronary Intervention,PCI)和冠状动脉旁路移植术(Coronary Artery Bypass Grafting,CABG)治疗术前SYNTAX积分32分的重度病变冠状动脉粥样硬化心脏病(Coronary Heart Disease,CHD)患者的临床效果及安全性。方法:纳入2017年3月6日至2017年5月20日在西京医院心血管内外科成功行CABG且术前SYNTAX积分32分的重度病变CHD患者50名和成功行PCI且术前SYNTAX积分32分的重度病变CHD患者50名,分为PCI组与CABG组。比较两组患者的一般基线资料和院内死亡发生情况,术后一年电话随访患者存活情况、病死原因、再次入院、心绞痛、心肌梗死、脑卒中等发生情况,通过SF-12量表和西雅图量表评估患者的生活质量的改善情况。结果:与CABG组相比,PCI组患者心率更低、住院时间更短、住院花费更少、有PCI史的患者比例更高,差异具有统计学意义(P0.05)。术后一年,两组患者心功能改善情况和主要不良心脑血管事件(major adverse cardiac and cerebrovascular events,MACCE)发生率、SF-12量表与西雅图心绞痛量表(Seattle Angina Questionnaire, SAQ)的各个维度评分比较差异均无统计学意义(P0.05)。结论:PCI与CABG治疗不同病变严重程度的冠心病患者的临床效果及安全性相当。     

Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease

Background

Endothelial dysfunction precedes coronary artery disease (CAD) and can be measured by peripheral arterial tonometry (PAT). We examined the applicability of PAT to detect a low risk of CAD in a chest pain clinic.

Methods

In 93 patients, PAT was performed resulting in reactive hyperaemia (RHI) and augmentation (AIx) indices. Patients were risk classified according to HeartScore, Diamond and Forrester pretest probability (DF), exercise testing (X-ECG), and computed tomography calcium scoring (CCS) and angiography (CTA). Correlations, risk group differences and prediction of revascularisation within 1 year were calculated.

Results

RHI correlated with HeartScore (r = − 0.21, p = 0.05), AIx with DF (r = 0.26, p = 0.01). However, both were not significantly different between normal and ischaemic X-ECG groups. In addition RHI and AIx were similar between low risk as compared with intermediate-to-high risk, based on risk algorithms (RHI: 1.98 (0.67) vs 1.94 (0.78); AIx: 0.0 (21) vs 5.0 (25); p = NS), or CCS and CTA (RHI: 1.99 (0.58) vs 1.89 (0.82); AIx: − 2.0 (24) vs 4.0 (25); p = NS). Finally, RHI and AIx failed to predict revascularisation (RHI: OR 1.42, CI 0.65–3.1; AIx: OR 1.02, CI 0.98–1.05).

Conclusions

PAT cannot detect a low risk of CAD, possibly because RHI and AIx versus X-ECG, CCS and CTA represent independent processes.     

Diagnostic approach in patients with angina and no obstructive coronary artery disease: emphasising the role of the coronary function test

BackgroundMany patients with angina do not have obstructive coronary artery disease (CAD), also referred to as “Ischaemia with No Obstructive Coronary Arteries“ (INOCA). Coronary vascular dysfunction is the underlying cause of this ischaemic heart disease in as much as 59–89% of these patients, including the endotypes of coronary microvascular dysfunction and epicardial coronary vasospasm. Currently, a coronary function test (CFT) is the only comprehensive diagnostic modality to evaluate all endotypes of coronary vascular dysfunction in patients with INOCA.ObjectiveIn this paper we discuss the relevance of performing a CFT, provide considerations for patient selection, and present an overview of the procedure and its safety.MethodsWe reviewed the latest published data, guidelines and consensus documents, combined with a discussion of novel original data, to present this point of view.ResultsThe use of a CFT could lead to a more accurate and timely diagnosis of vascular dysfunction, identifies patients at risk for cardiovascular events, and enables stratified treatment which improves symptoms and quality of life. Current guidelines recommend considering a CFT in patients with INOCA and persistent symptoms. The safety of the procedure is comparable to that of a regular coronary angiography with physiological measurements. Non-invasive alternatives have limited diagnostic accuracy for the identification of coronary vascular dysfunction in patients with INOCA, and a regular coronary angiography and/or coronary computed tomography scan cannot establish the diagnosis.ConclusionsA complete CFT, including acetylcholine and adenosine tests, should be considered in patients with INOCA.Supplementary InformationThe online version of this article (10.1007/s12471-020-01532-9) contains supplementary material, which is available to authorized users.     

Addition of FFRct in the diagnostic pathway of patients with stable chest pain to reduce unnecessary invasive coronary angiography (FUSION): Rationale and design for the multicentre,randomised, controlled FUSION trial

BackgroundCoronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome.MethodsThe FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days.ConclusionThe FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme ‘Potentially Promising Care’ and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.Supplementary InformationThe online version of this article (10.1007/s12471-022-01711-w) contains supplementary material, which is available to authorized users.     

Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease

Number and function of endothelial progenitor cells (EPCs) are down-regulated in patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a signal and adaptor protein that regulates survival of mature endothelial cells and vascular development.Here we show that EPC dysfunction in patients with CAD is paralleled by down-regulation of ILK while restoration of ILK expression rescues the migratory defect of CAD-EPCs. Human EPCs transduced with dominant-negative ILK (DN-ILK) display significantly reduced expression of CD34⁺/VEGFR-2⁺, DiI-Ac-LDL uptake, and Ulex europaeus lectin binding. Mechanistically, DN-ILK-transfected EPCs are characterized by decreased proliferation, while proliferation is increased in wild-type ILK-transfected EPCs. These effects are paralleled by changes in cyclin D1 expression, colony forming units, and cytoskeletal rearrangement. Functionally, ILK is necessary and sufficient for SDF-1-triggered migration and adhesion in EPCs.These data extend current knowledge about the role of ILK in EPC biology and implicate ILK as a therapeutic target in CAD.     

冠心病患者运动致QRS延长的临床意义

为探讨冠心病病人由于急性心肌缺血对ＱＲＳ持续时间变化的影响及其意义。本文收集了５３例病人,均进行运动试验和冠脉造影,其中２０例经冠脉造影排除心病,其他３３例经冠脉造影确定为冠心病。结果运动使冠脉正常者ＱＲＳ持续时间缩短,而使冠心病者ＱＲＳ持续时间延长。     

A potential oral microbiome signature associated with coronary artery disease in Tunisia

The coronary artery disease (CAD) is a chronic inflammatory disease involving genetic as well as environmental factors. Recent evidence suggests that the oral microbiome has a significant role in triggering atherosclerosis. The present study assessed the oral microbiome composition variation between coronary patients and healthy subjects in order to identify a potential pathogenic signature associated with CAD. We performed metagenomic profiling of salivary microbiomes by 16S ribosomal RNA (rRNA) next-generation sequencing. Oral microbiota profiling was performed for 30 individuals including 20 patients with CAD and ten healthy individuals without carotid plaques or previous stroke or myocardial infarction.We found that oral microbial communities in patients and healthy controls are represented by similar global core oral microbiome. The predominant taxa belonged to Firmicutes (genus Streptococcus, Veillonella, Granulicatella, Selenomonas), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Rothia), Bacteroidetes (genus Prevotella, Porphyromonas), and Fusobacteria (genus Fusobacterium, Leptotrichia). More than 60% relative abundance of each sample for both CAD patients and controls is represented by three major genera including Streptococcus (24.97 and 26.33%), Veillonella (21.43 and 19.91%), and Neisseria (14.23 and 15.33%).Using penalized regression analysis, the bacterial genus Eikenella was involved as the major discriminant genus for both status and Syntax score of CAD. We also reported a significant negative correlation between Syntax score and Eikenella abundance in coronary patients’ group (Spearman rho = −0.68, P=0.00094).In conclusion, the abundance of Eikenella in oral coronary patient samples compared with controls could be a prominent pathological indicator for the development of CAD.     

原发性高血压合并冠心病患者血清CRP的变化

目的:探讨原发性高血压合并不同类型冠心病患者血清C-反应蛋白(CRP)的变化及其意义。方法:用全自动生化分析仪检测71例原发性高血压患者和28例健康对照组人群的血清CRP水平,所有研究对象均行选择性冠状动脉造影检查。将原发性高血压组病人根据冠脉造影检查分为单纯原发性高血压组(EH),原发性高血压合并稳定性心绞痛组(EH+SAP)、原发性高血压合并不稳定心绞痛组(EH+UAP)、原发性高血压合并心肌梗死组(EH+MI),比较各组患者血清CRP水平的差异。结果:①与对照组比较,EH组及EH合并CAD各组患者血清CRP均显著升高(P0.05);②与EH组比较,EH+UAP和EH+MI组血清CRP水平均显著升高(P0.01);③与EH+SAP组比较,EH+AMI组和EH+UAP组血清CRP水平均显著升高(P0.01)。结论:冠心病合并原发性高血压患者血CRP水平与冠状动脉病变程度与斑块稳定程度存在正相关性。     

炎症与动脉粥样硬化及冠状动脉疾病的关系

炎症在冠状动脉疾病和其他动脉粥样硬化性疾病中起着重要作用.在动脉粥样硬化早期病变处存在大量的免疫细胞,它们所分泌的一系列细胞因子加速病变的进程,激活炎症反应导致急性冠脉综合症的发生.动脉粥样硬化,是冠状动脉疾病的主要病因,是一种炎性疾病,炎症因子参与到免疫反应过程中,使得动脉壁处的病变得以发生、蔓延和活化.     

Increased endoplasmic reticulum stress and Nrf2 repression in peripheral blood mononuclear cells of patients with stable coronary artery disease

Endoplasmic reticulum (ER) stress is involved in the pathophysiology of atherosclerosis. Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER that initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signaling is induced. We evaluated: (1) the UPR and ER-initiated apoptotic signaling in peripheral blood mononuclear cells (PBMCs) of stable coronary artery disease (CAD) patients; (2) PBMC content of oxidation products of phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC); (3) the possible origin of oxPAPC in PBMCs; and (4) the expression of nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE), a cellular defense mechanism. Twenty-nine CAD patients and 28 matched controls were enrolled. Expression of glucose-regulated protein 78 kDa (GRP78/BiP), as a representative of the UPR, and of C/EBP homologous protein (CHOP), as a representative of ER apoptosis, was significantly higher in CAD than in controls (p<0.01). Concentrations of oxPAPC in PBMCs, in plasma, and in low-density lipoprotein (LDL) were significantly higher in CAD compared to controls (p<0.01). The oxPAPC in PBMCs may derive from circulating ox-LDL. Nrf2/ARE gene expression and circulating and cellular glutathione were significantly lower in CAD compared to controls (p<0.01). In in vitro studies, increasing amounts of oxPAPC induced a dose-dependent increase in CHOP and apoptosis-related protein expression (p<0.01) and a progressive decrease in Nrf2/ARE gene expression (p<0.01). In PBMCs of CAD patients there is an activation of the UPR and ER-initiated apoptotic signaling, possibly related to an abnormal concentration of oxPAPC in PBMCs.     

Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease

BACKGROUND: Intra-peritoneal adipose tissue is recognized as a predictor of metabolic syndrome and may contribute to the risk for cardiovascular disease by the production of adipocytokines, including adiponectin. Nevertheless, there is no knowledge on whether other visceral depots of adipose tissue, including the epicardial fat, have any metabolically active role, including production of adiponectin. AIM OF THE STUDY: We sought to evaluate adiponectin protein expression in epicardial adipose tissue in vivo both in patients with severe coronary artery disease (CAD) and in subjects without CAD. METHODS: Twenty-two patients were enrolled for the study. We selected 16 patients who underwent elective coronary artery bypass graft surgery for critical CAD, 5 who underwent surgery for valve replacement and 1 for correction of an interatrial defect. Epicardial adipose tissue biopsy samples were obtained before the initiation of cardiopulmonary bypass. Adiponectin protein level in epicardial adipose tissue was evaluated by Western blotting. RESULTS: Adiponectin protein value, expressed as adiponectin/actin ratio, in epicardial adipose tissue was significantly lower in patients with severe CAD than in those without CAD (1.42 +/- 0.77 vs 2.36 +/- 0.84 p = 0.02, 95% CI 0.64-1.74). CONCLUSIONS: This study showed for the first time that human epicardial adipose tissue expresses adiponectin. Adiponectin expression is significantly lower in epicardial fat isolated from patients with CAD.     

Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease

To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.     

Autoantibodies against oxidized LDL are associated with severe chest pain attacks in patients with coronary heart disease

Autoantibodies against oxidized low-density lipoprotein (oxLDL) predict the progression of atherosclerosis. Several studies have shown that oxLDL is present in atherosclerotic lesions and that several factors present in active atherosclerotic plaques can oxidatively modify LDL. Oxidation of LDL induces production of autoantibodies against oxLDL (oxLDLab) that can be measured using an EIA test. Our aim was to see whether oxLDLab are associated with severe chest pain attacks in coronary heart disease (CHD) patients. Patients having two- or three-vessel CHD, as assessed by coronary angiography, and their siblings were recruited into the study (n = 568, mean age 55.8 years, range 29.3–83.2 years). Nondiabetic patients having a history of severe chest pain attacks had significantly higher oxLDLab levels (0.611 ± 0.56) than those who did not have a history of severe chest pain attacks (0.487 ± 0.40) (p = 0.027), even though age, cholesterol level, body mass index, and blood pressure were similar in both groups. However, no difference was found in oxLDLab levels in diabetic patients with or without a history of severe chest pain attacks. Increased levels of oxLDL autoantibodies are associated with severe chest pain attacks in nondiabetic patients with CHD.     

Detection of mtDNA with 4977 bp deletion in blood cells and atherosclerotic lesions of patients with coronary artery disease

Recent evidence suggests that somatic mutations in nuclear and mitochondrial DNA accumulated during aging, may significantly contribute to the pathogenesis of chronic-degenerative illness such as coronary artery disease (CAD). Mitochondrial DNA with 4977 bp deletion mutation (mtDNA4977) is a common type of mtDNA alteration in humans. However, little attempt has been made to detect the presence of mtDNA4977 deletion in cells and tissues of cardiovascular patients. This study investigated the presence of mtDNA4977 in blood samples of 65 cardiovascular patients and 23 atherosclerotic plaques of human coronaries with severe atherosclerosis. Moreover, the presence of the deletion has been investigated in blood cells from 22 healthy age-matched subjects. The detection of mtDNA4977 has been performed by using a nested polymerase chain reaction (PCR) protocol and normalized to wild-type mtDNA. A significant higher incidence of mtDNA4977 was observed in CAD patients with respect to healthy subjects (26.2% versus 4.5%; P=0.03). Furthermore, the relative amount of the deletion was significantly higher in the patients compared to the control group (P=0.02). The mtDNA4977 was detected in 17 of the 65 patients blood samples (26.2%) and deletion levels ranged from 0.18 to 0.46% of the total mtDNA (mean: 0.34+/-0.02%). For what concerns atherosclerotic lesions, 5 patients (21.7%) showed the deletion ranging from 0.13 to 0.45% of the total mtDNA (mean: 0.35+/-0.06%). In both samples from patients, the incidence and the relative amount of mtDNA4977 was not significantly influenced by atherogenic risk factors and clinical parameters. The obtained results may suggest that the increase of oxidative stress in cardiovascular disease may be responsible for the accumulation of mtDNA damage in coronary artery disease patients.     

Alkaline phosphatase-to-albumin ratio as a novel predictor of long-term adverse outcomes in coronary artery disease patients who underwent PCI

Background: Alkaline phosphatase (ALP) and albumin (ALB) have been shown to be associated with coronary artery disease (CAD), and it has been reported that alkaline phosphatase-to-albumin ratio (AAR) is associated with the liver damage and poorer prognosis of patients with digestive system malignancy. Moreover, several previous studies showed that there was a higher incidence of malignancy in CAD patients. However, to our knowledge, the relationship between AAR and long-term adverse outcomes in CAD patients after undergoing percutaneous coronary intervention (PCI) has not been investigated. Therefore, we aim to access the relation between AAR and long-term adverse outcomes in post-PCI patients with CAD.Methods: A total of 3378 post-PCI patients with CAD were enrolled in the retrospective Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-ZZ) study from January 2013 to December 2017. The median duration of follow-up was 37.59 ± 22.24 months. The primary end point was long-term mortality including all-cause mortality (ACM) and cardiac mortality (CM). The secondary end points were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs).Results: Kaplan–Meier analyses showed that an increased AAR was positively correlated with incidences of long-term ACM (log-rank, P=0.014), CM (log-rank, P=0.011), MACEs (log-rank, P=0.013) and MACCEs (log-rank, P=0.006). Multivariate Cox regression analyses showed that the elevated AAR was an independent predictor of long-term ACM (adjusted HR = 1.488 [1.031–2.149], P=0.034), CM (adjusted HR = 1.837 [1.141–2.959], P=0.012), MACEs (adjusted HR = 1.257 [1.018–1.551], P=0.033) and MACCEs (adjusted HR = 1.237 [1.029–1.486], P=0.024).Conclusion: An elevated AAR is a novel independent predictor of long-term adverse outcomes in CAD patients following PCI.