Coronary Artery Disease Subjects Research Articles

Mediation analysis for the relationship between dyslipidemia and coronary artery disease via hypersensitive C-reactive protein in a case-control study.

The pathological basis of coronary artery disease (CAD) is atherosclerosis which is associated with inflammation and dyslipidemia. However, the involvement of hypersensitive C-reactive protein (hs-CRP) in lipid metabolism and how it affects the pathogenesis of CAD is uncertain. To explore whether the relationship between dyslipidemia and CAD is partly mediated by hs-CRP levels. Three hundred fifteen pairs of randomly sexand age-matched CAD and non-CAD subjects collected from Zhongda Hospital Affiliated to Southeast University were involved in the final analysis. We gathered information about each subjects clinical history as well as their results of detected hs-CRP and lipid levels. Linear regression analysis was used to determine the association between dyslipidemia and hs-CRP levels in which univariate and multivariate logistic regression analyzes were performed to determine the relationship between hs-CRP levels and CAD as well as dyslipidemia and CAD. Mediation analysis was used to evaluate whether hs-CRP levels act as a mediator of the relationship between dyslipidemia and CAD. Dyslipidemia and hs-CRP levels were significantly associated with an increased risk of CAD, with β = 0.594 (P = 0.001) and β = 0.016 (P = 0.024), respectively, and there was a correlation between dyslipidemia and hs-CRP levels (β = 3.273, P = 0.004). Mediation analysis results revealed that the correlation between dyslipidemia and CAD was 8.27% mediated by hs-CRP levels with a direct effect of 0.621 and an indirect effect of 0.056. Hs-CRP levels played a partial mediation role in the association between dyslipidemia and CAD.

Early repolarization pattern associated with coronary artery disease and increased the risk of cardiac death in acute myocardium infarction

BackgroundEarly repolarization pattern (ERP) was associated with sudden cardiac death in recent studies. However, the associations between ERP and coronary artery disease (CAD), and ERP and cardiac death caused by acute myocardial infarction (MI) remains unclear.MethodsWe retrospectively enrolled consecutive 1,545 CAD patients and 908 non‐CAD subjects as control group which were confirmed by coronary angiograph. The CAD patients include stable CAD, acute MI patients, and old MI patients. Multivariate logistic regression was employed to evaluate the relationship between ERP and CAD, and ERP and cardiac death caused by acute MI.ResultsOf the 1,545 CAD subjects, there were 1,029 stable CAD patients, 404 acute MI patients, and 112 old MI patients. The incidence of ERP was much higher among patients with CAD than without CAD subjects (20.1% vs. 6.2%, p < .001) after adjusting for major cardiovascular risk factors. No significant correlation was observed between lead region of ERP on 12‐lead ECG and single abnormal artery. Of the 404 acute MI patients, 342 patients survived and 62 patients died. Incidence of ERP was higher in non‐survivor than survivor patients with acute MI (24.2% vs. 17.5%, p = .006) after adjustment for major cardiovascular risk factors.ConclusionThe incidence of ERP was higher in CAD patients than subjects without CAD and in non‐survivor patients than survivor patients with acute MI. The lead region of ERP on 12‐lead ECG was not associated with single abnormal coronary artery.

Autoregressive Whitening Filtering of Phonocardiography Signals for Detection of Coronary Artery Disease

Background: Narrowing of the coronary arteries, which defines coronary artery disease (CAD), can be discovered through phonocardiography (PCG) analysis. Increased power of frequencies below 200 Hz in the diastole has been associated with CAD, and can be used to distinguish CAD from NonCAD patients. However, spectral roll off is steep (~40 dB/dec), and spectral leakage might mask the weak CAD-related signal.Methods: PCGs from 1168 subjects, 213 CAD and 955 NonCAD, were pooled from three studies. The average power spectral density (PSD) of diastole segments for NonCAD subjects was found, and an auto-regressive (AR) model of this PSD was constructed. The inverse of the corresponding filter was used for whitening.Results: A single iteration of whitening filtering was insufficient to make the PSD white for 5-1000 Hz. Two iterations of whitening filtering with an order of 6-10 were required to reach a plateau of maximal whitening with a spectral flatness measure close to 1 in the frequency band 5-1000 Hz. The whitening process revealed additional PSD differences between CAD and NonCAD subjects for the mid-diastole segment.Conclusion: Whitening of diastole PCG segments emphasized the difference between CAD and NonCAD patients.

Serum Level of Interleukin-33, C-Reactive Protein, and Troponin in Iraqi Coronary Artery Disease Patients

Coronary artery disease (CAD) is a condition of an inadequate supply of oxygenated blood to a portion of the myocardium. It typically occurs when there is an imbalance between supply and demand of myocardial oxygen. The most common cause of myocardial ischemia is atherosclerotic disease of an epicardial coronary artery or arteries which is sufficient to cause a regional reduction in myocardial blood flow and inadequate perfusion of the myocardium supplied by the involved coronary artery. Fifty CAD subjects (23 females and 27 males) were enrolled in this study in addition to thirty healthy control subjects (13 female and 17 male). This study aimed to measure the serum levels of interleukin IL- 33, C- reactive protein and troponin in CAD and their association with lipid profile by using enzyme-linked immune sorbent assay (ELISA). T results showed that high-density lipoprotein (HDL) was statistically high while differences in cholesterol, triglyceride and low-density lipoprotein (LDL) were statistically non-significant between CAD patients and controls. Moreover, the serum level of IL-33 and CRP were statistically higher in patients than controls, while troponin levels were not significantly different. In addition, the present study demonstrates that IL-33, CRP, and Troponin were not associated with lipid profile. The relationship of IL-33 with CRP and troponin was non-significant.

Patients with Abdominal Aortic Aneurysm Are at Higher Risk of Cancer and Metastasis

Background: Some studies focusing on the endovascular repair of abdominal aortic aneurysms (AAA) have demonstrated that cancer is often found in such patients. Retrospective investigations have also indicated that AAA patients have an increased risk of cancer. However, the incidence rate of cancer and survival rate in patients with AAA compared to the population remains unknown. Methods: We conducted a prospective, single center, non-randomized, comparative cohort study including 223 AAA patients and 1000 Coronary artery disease (CAD) patients enrolled in our department between 01/01/2008 and 31/12/2011 with annual follow-up until 31/12/2018. Based on statistics from the Belgian cancer registry Belgium, the incidence rate of cancer was calculated for both men and women in the general population. The primary endpoint was the cumulative incidence rate of cancer in all three groups and the secondary endpoint was overall survival. Results: After nine years of follow-up, the cancer incidence was 30·1% (95%CI: 21·6-39·3%) in AAA patients and 23·5% (95%CI: 20·0-27·1%) in CAD subjects, markedly higher than the Walloon population (17·4%). Moreover, the development of metastases among patients with AAA was higher compared to CAD patients (38·7% vs.18·6%, P=0·03). In terms of overall survival, the proportion of cancer deaths in AAA patients was twice as high as in CAD patients. Conclusions: This study confirms an increased incidence of cancers and decreased survival in AAA patients compared to the general population. Funding Statement: This work was supported by the European Program FP7 “Fighting aneurysmal diseases” (no. 200647). Audrey Courtois and Jacobine Munten were funded by the Aneurysmal Pathology Foundation. Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: The study was designed and conducted within the framework of the European program “Fighting Aneurysmal Disease (FAD; B70720095774 and B70720095773 9)” approved by the ethics committee (n°200647). All the participants were instructed on the study objectives and provided informed consent. The study was approved by the ethics board of the University hospital of Liege.

Automated Coronary Artery Disease Detection using RQA Features and Quadratic Support Vector Machine

One of the major causes of death globally due to heart disease is the coronary artery disease (CAD). Due to CAD the blood flow to the cardiac muscle is reduced. The progression of this process eventually causes Myocardial Infarction (MI) that result in sudden death. Hence the detection of CAD at early phase is essential. The electrocardiogram (ECG) is mainly used to capture the abnormal cardiac activity for CAD. But the difficulties in manual interpretation of ECG signal leads to error in CAD detection. To overcome the difficulty in CAD diagnostic task, we have proposed a computer aided methodology using the heart rate variability signal (HRV) for auto diagnosis of CAD and Normal heart condition. The hidden characteristics of HRV signal are identified through Recurrence Plot (RP) and the hidden information is quantified by Recurrence quantification analysis (RQA). The extracted RQA based nonlinear features are analyzed for their clinical significance. The set the effective features are used for classification and subjected to three types of Support vector machine (SVM) classifier to discriminate CAD and the normal heart condition. The ECG database of CAD and normal subjects are taken from Physio.net database to obtain the experimental results. The highest diagnostic ability of the classifier is obtained by quadratic SVM with the accuracy of 98.83% where as the linear and cubic SVM classifier provide 97.22 % and 98.37 % classification accuracy respectively.

1D-CADCapsNet: One dimensional deep capsule networks for coronary artery disease detection using ECG signals

PurposeCardiovascular disease (CVD) is a leading cause of death globally. Electrocardiogram (ECG), which records the electrical activity of the heart, has been used for the diagnosis of CVD. The automated and robust detection of CVD from ECG signals plays a significant role for early and accurate clinical diagnosis. The purpose of this study is to provide automated detection of coronary artery disease (CAD) from ECG signals using capsule networks (CapsNet). MethodsDeep learning-based approaches have become increasingly popular in computer aided diagnosis systems. Capsule networks are one of the new promising approaches in the field of deep learning. In this study, we used 1D version of CapsNet for the automated detection of coronary artery disease (CAD) on two second (95,300) and five second-long (38,120) ECG segments. These segments are obtained from 40 normal and 7 CAD subjects. In the experimental studies, 5-fold cross validation technique is employed to evaluate performance of the model. ResultsThe proposed model, which is named as 1D-CADCapsNet, yielded a promising 5-fold diagnosis accuracy of 99.44% and 98.62% for two- and five-second ECG signal groups, respectively. We have obtained the highest performance results using 2 s ECG segment than the state-of-art studies reported in the literature. Conclusions1D-CADCapsNet model automatically learns the pertinent representations from raw ECG data without using any hand-crafted technique and can be used as a fast and accurate diagnostic tool to help cardiologists.

Dysregulation of autophagy-related lncRNAs in peripheral blood of coronary artery disease patients

Coronary artery disease (CAD) as a major cause of death has been associated with dysregulation of several processes among them is autophagy. In the current study, we assessed expression of autophagy related gene 5 (ATG5) and three ATG5-associated long non-coding RNAs (lncRNAs Chast, HULC and DICER1-AS1) in the peripheral blood of patients with premature CAD and healthy subjects. Expression levels of ATG5, Chast, HULC and DICER1-AS1 were significantly lower in peripheral blood of CAD cases compared with healthy subjects. Receiver Operating Characteristic (ROC) curve analysis showed that HULC and DICER1-AS1 can properly differentiate CAD patients from healthy subjects (area under curve (AUC) values of 0.90 and 0.87, respectively). Expression levels of ATG5 and Chast were inversely correlated with FBS levels (r = −0.41, P < 0.0001 and r = −0.38, P < 0.0001 respectively) but no other biochemical factors. Expression of DICER1-AS1 was inversely correlated with FBS (r = −0.54, P < 0.0001), TG (r = −0.29, P < 0.0001) and TG/HDL ratio (r = −0.27, P < 0.0001). Expression of HULC was inversely correlated with age (r = −0.24, P < 0.0001), FBS (r = −0.62, P < 0.0001) and TG (r = −0.31, P < 0.0001). There were significant pairwise correlations between expression levels of all genes. The most robust correlations were detected ATG5 and Chast (r = 0.81, P < 0.0001) and between DICER1-AS1 and HULC (r = 0.75, P < 0.0001). The current study further verified associations between dysregulation of autophagy and CAD. Moreover, our results indicate appropriateness of two autophagy-related lncRNAs for differentiation of CAD status.

Change in matrix metalloproteinase 2, 3, and 9 levels at the time of and after acute atherothrombotic myocardial infarction.

Elevated measures of matrix metalloproteinases (MMPs) are associated with acute myocardial infarction (MI), but it is not known how long these changes persist post-MI or if these measures differ between atherothrombotic versus non-atherothrombotic MI. MMPs-2, 3, and 9 were measured in 80 subjects with acute MI (atherothrombotic and non-atherothrombotic MI) or stable coronary artery disease (CAD). Measurements were made at, the time of acute MI, and > 3-month following acute MI (quiescent phase). Outcome measures were compared between groups and between time of acute MI and quiescent post-MI follow-up using Wilcoxon's and repeated measures analysis of variance. Forty-nine subjects met the criteria for acute MI with clearly defined atherothrombotic (n = 22) and non-atherothrombotic (n = 12) subsets. Fifteen subjects met criteria for stable CAD. MMP-3 was higher in acute MI versus stable CAD subjects at the time of acute MI: (453 vs. 217pg/mL, p = 0.010) but not at quiescent phase follow-up (p > 0.05). MMP-9 was higher in acute MI versus stable CAD subjects at the time of acute MI: (412 vs. 168pg/mL, p = 0.002) but not at the quiescent phase follow-up (p > 0.05). MMP-9 was higher at the time of acute MI versus quiescent phase follow-up in acute MI (412 vs. 213pg/mL, p = 0.001) and atherothrombotic MI specifically (458 vs. 212pg/mL, p = 0.001). No difference in MMP-2, 3, or 9 was observed between atherothrombotic versus non-atherothrombotic MI subgroups. MMPs-3 and 9 are significantly elevated in acute MI verses stable CAD subjects at time of acute MI but not different at quiescent phase follow-up. MMP-9 is elevated at the time of acute MI and specifically in acute atherothrombotic MI at time of MI versus quiescent phase follow-up.

Comparison of Tumor Necrosis Factor-α Level in Coronary Artery Disease and Coronary Slow Flow of Thrombolysis in Myocardial Infarction

BACKGROUND: Tumor necrosis factor (TNF)-α, an important primary pro-inflammatory cytokine, has a crucial role in the pathogenesis of atherosclerosis. Since the pathophysiological mechanism of coronary slow flow (CSF) is not fully understood, we investigated the level of TNF-α in coronary artery disease (CAD), CSF and healthy subjects.METHODS: This study was conducted in cross-sectional design involving 16 CAD, 18 CSF and 18 healthy subjects. Coronary angiography was recorded at the left anterior oblique, cranial, right anterior oblique, caudal, and horizontal positions. The flow in coronary arteries of the subjects were assessed using Thrombolysis in the Myocardial Infarction (TIMI) frame count method. Peripheral blood-derived serum was collected and level of TNF-α was determined by using highly sensitive enzymelinked immunosorbent assay (ELISA).RESULTS: No significant difference in level of TNF-α in CAD, CSF and healthy subjects (2.72±2.64 pg/mL, 1.88±0.8 pg/mL, 1.64±0.35 pg/mL, respectively) (p=0.087). In addition, there was no correlation between the concentration of TNF-α and TIMI frame count (r&lt;0.2, p&gt;0.05).CONCLUSION: There was no significant difference of TNF-α level in CAD, CSF and healthy subjects. In addition, there was no correlation between the TNF-α level with TIMI frame count as well. Nevertheless, further clinical studies with more subjects are needed.KEYWORDS: TNF-alpha, coronary artery disease, coronary slow flow

CORONARY HEART DISEASE DETECTION USING NONLINEAR FEATURES AND ONLINE SEQUENTIAL EXTREME LEARNING MACHINE

In this paper, we propose an automated approach that combines the generalized discriminant analysis (GDA) as feature reduction scheme with radial basis function (RBF) kernel and the online sequential extreme learning machine (OSELM) having Sigmoid, Hardlim, RBF and Sine activation function as binary classifier for detection of congestive heart failure (CHF) and coronary artery disease (CAD). For this analysis, 13 nonlinear features as Correlation Dimension (CD), Detrended Fluctuation Analysis (DFA) as DFA-[Formula: see text]1 and DFA-[Formula: see text]2, Bubble Entropy (BBEn), Sample Entropy (SampEn), Dispersion Entropy (DISEn), Lempel–Ziv Complexity (LZ), Sinai Entropy (SIEn), Improved Multiscale Permutation Entropy (IMPE), Hurst Exponent (HE), Permutation Entropy (PE), Approximate Entropy (ApEn) and Standard Deviation (SD1/SD2) were extracted from Heart Rate Variability (HRV) signals. For validation of proposed method, HRV data were obtained from standard database of normal sinus rhythm (NSR), CHF and CAD subjects. Numerical experiments were done on the combination of database sets such as NSR-CAD, CHF-CAD and NSR-CHF subjects. The simulation results show a clear difference in combination of database sets by using GDA having RBF, Gaussian kernel function and OSELM binary classifier having Sigmoid, RBF and Sine activation function and achieved an accuracy of 98.17% for NSR-CAD, 100% for NSR-CHF and CAD-CHF subjects.

High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study

Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited. In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM). Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n=150 cases) and history of CV events (CVE, n=85 cases) in an observational cohort (CODAM, n=574, 59.6±0.3yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism. HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P<.05) and CVE (ORs 0.61 to 0.68, P<.05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction=.074 and .034, respectively), but not in those with NGM. HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.

DNA methylation of antisense noncoding RNA in the INK locus (ANRIL) is associated with coronary artery disease in a Chinese population

To explore the association between methylation of antisense non-coding RNA in the INK4 locus (ANRIL) and coronary artery disease (CAD) development. Methylation levels of ANRIL in 100 subjects with CAD and 100 controls were quantitatively analyzed using Sequenom MassARRAY. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify novel pathways. Our analyses indicated that 7 to 8 CpG sites within the 2nd CpG island located upstream of ANRIL, also known as cyclin-dependent kinase inhibitor 2B – antisense 1 (CDKN2B-AS1), are hyper-methylated in CAD subjects compared to controls (p = 0.034). The 40th CpG site within the 2nd CpG island located upstream of CDKN2B-AS1 was methylated to a lesser extent in CAD subjects compared to controls (p = 0.045). Both Pearson and Spearman analyses indicated that methylation levels were significantly associated with total cholesterol (r = 0.204, p = 0.004), fasting high-density lipoprotein cholesterol (r = 0.165, p = 0.020), and fasting low-density lipoprotein cholesterol (r = 0.265, p = 0.000). KEGG pathway analysis revealed a significant enrichment of genes associated with the tumor necrosis factor (TNF) signaling pathway. Among them, CCAAT/enhancer binding protein (C/EBPβ) was identified as a key transcription factor that promotes expression of CDKN2B-AS1 through promotor interaction. DNA methylation of the ANRIL promoter was significantly associated with CAD development in our study. Our analyses suggest that C/EBPβ is a key transcription factor that promotes CDKN2B-AS1 expression by directly interacting with the gene promotor mediated by TNF signaling.

P5245Cost-saving diagnosis approach by artificial intelligence tool in patients with suspected coronary artery disease. The co-operative ARTICA registry database

Abstract Background Although coronary tomographic angiography (CTA) has shown promise as a “gatekeeper” to invasive coronary angiography (ICA) in longitudinal cohort studies, it remains unknown whether the strategy of direct initial performance of CTA is cost-effective when compared with selected exercise treadmill testing (ETT) +/− functional cardiac imaging strategies in patients with suspected coronary artery disease (CAD). An innovative artificial intelligence (AI) Decision Support System (DSS) ESC guidelines based has been used at point of care for evaluating subjects with stable chest pain (SCP). Purpose The objective was to verify the cost-saving effect of the robotic AI DSS vs direct CTA by human standard care (SD) for diagnosing CAD in subjects presenting with SCP. Methods From October 2016 over three hospitals, 1017 subjects, 620 males, age 62±11 years, with clinically SCP being referred for CTA by SD received also a same day pre-scan AI DSS administration. All patients did not demonstrate significant CAD at CTA. CTA/ICA, or exercise treadmill test (ETT)/ stress echocardiography (SE), gated myocardial perfusion scintigraphy (gMPS) or Follow up/No tests (FNT) strategies by AI DSS were analyzed and compared to direct CTA SD. Pre-test likelihood (pt-lk) of CAD consider clinical risk factors into the model. Sensitivity and specificity of non-invasive diagnostic tests within our model were based upon a bivariate analysis of data from published multicenter trials. Costs of procedures were calculated by the sum of technical and professional components. Probabilistic sensitivity analysis was conducted to assess the impact of uncertainty in model parameters. Results The direct approach used performing direct CTA strategy by SD in all subjects costed 406.800 €. Costs of each procedure and distribution of AI DSS outputs are shown in the Table. Across the range of pt-lk of CAD, total costs of AI DSS strategy resulted 146.030€ with −65% vs SD approach. AI DSS tests distribution and costs pt-lk (pt/%) FNT (0€) ETT (90€) SE (350€) Stress gated MPS (750€) CCTA (400€) ICA (3.000€) High (29/2.8) 0 0 1 2 0 26 Int (371/36.5) 259 5 51 48 7 1 Low (612/60.7) 595 2 2 0 13 0 Total costs (€) 0 630 18,900.00 37,500.00 8,000.00 81,000.00 Conclusion These results from ARTICA registry seem to demonstrate that AI DSS is extremely cost-saving in subjects with stable chest pain across the whole range of pt-lk of CAD.

Visceral Adiposity Index as an Independent Marker of Subclinical Atherosclerosis in Individuals Prone to Diabetes Mellitus.

Aims: The visceral adiposity index (VAI) has been proposed as an estimate of visceral adipose tissue (VAT) mass and as an indicator of VAT dysfunction. Both parameters are associated with cardiometabolic risk, including insulin resistance. In this study, we investigated whether VAI is associated with subclinical atherosclerosis in subjects who were free of cardiovascular disease but were at risk of developing diabetes mellitus.Methods: A total of 731 adults with a median age of 47 years old without diabetes mellitus were included in this cross-sectional study. The anthropometric data, blood pressure, and lipid profiles of 398 women and 333 men were measured. All subjects underwent an oral glucose tolerance test, and carotid intima–media thickness (cIMT) was evaluated by ultrasound. Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR).Results: VAI and HOMA-IR (βst = 0.44, p < 0.0001), VAI and cIMT (βst = 0.17, p < 0.0001), and HOMA-IR and cIMT (βst = 0.09, p = 0.0127) were correlated with each other. After adjusting for cofounding variables, VAI is still correlated with HOMA-IR (βst = 0.42, p < 0.0001). Furthermore, VAI (βst = 0.07, p = 0.0392) but not HOMA-IR (βst = 0.03, p = 0.37) was correlated with cIMT independently of other established cardiovascular risk factors.Conclusion: The calculation of VAI may provide a better estimation of subclinical atherosclerosis than the calculation of HOMA-IR.

Serum Levels of Carbamylated LDL and Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Are Associated with Coronary Artery Disease in Patients with Metabolic Syndrome.

Background and objectives: Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) has been recognized as the primary receptor for carbamylated low-density lipoproteins (cLDL) and is increasingly being viewed as a critical mediator of vascular inflammation and atherosclerosis. The aim of the current study was to evaluate the possible role of circulating cLDL and soluble LOX-1 (sLOX-1) as potential biomarkers of metabolic syndrome (MetS) as well as of coronary artery disease (CAD) among MetS patients. Materials and Methods: The serum levels of cLDL and sLOX-1 were measured by ELISA in 30 MetS patients without CAD, 30 MetS patients with CAD, and 30 healthy controls. Results: Patients with MetS had significantly higher serum levels of both cLDL and sLOX-1 than the healthy controls but lower in comparison to MetS + CAD subjects. Serum sLOX-1 concentration correlated significantly with fasting glucose (rs = 0.414, p = 0.001) and high-density lipoprotein (HDL)-cholesterol (rs = −0.273, p = 0.035) in the whole MetS cohort, whereas it correlated with cLDL only in the MetS + CAD subgroup (rs = 0.396, p = 0.030). The receiver-operating characteristic (ROC) curves of cLDL and sLOX-1 for MetS diagnosis had area under the curve (AUC) values of 0.761 and 0.692, respectively. AUC values of cLDL and sLOX-1 for CAD diagnosis among MetS patients were 0.811 and 0.739. Elevated serum levels of cLDL and sLOX-1 were associated with a higher risk of MetS development [odds ratio (OR) 24.28, 95% confidence interval (CI): 5.86–104.61, p < 0.001 and OR 4.75; 95% CI: 1.58–14.25, p = 0.009] as well as with presence of CAD among MetS subjects (OR 11.23; 95% CI: 3.10–40.71, p < 0.001 and OR 4.03; 95% CI: 1.73–11.84, p = 0.019, respectively). Conclusions: The present study underscores the potential of cLDL and sLOX-1 as promising biomarkers for diagnosis and risk assessment of MetS and CAD among the MetS population.

MicroRNA-copy number variations in coronary artery disease patients with or without type 2 diabetes mellitus

Background An important cause of Coronary Artery Disease (CAD) is Type 2 Diabetes Mellitus (T2DM). The aim of this study was the evaluation of copy number variations (CNVs) of hsa-miR-93, hsa-miR-122, hsa-miR-192 in CAD patients with or without T2DM. Methods CNVs of three micro-RNAs in 50 CAD patients and 50 non-CAD subjects both with and without diabetes were evaluated by real-time PCR and compared in three comparison groups namely 1, 2 and 3 (including comparison between CAD and non-CAD, diabetic CAD and non-diabetic CAD and between diabetic CAD and diabetic non-CAD subjects, respectively). Results There were significant differences in CNVs of hsa-miR-93 between cases and controls in comparison groups 1 and 3 (p = .0310 and .0232, respectively), for hsa-miR-122 in all comparison groups, and for hsa-miR-192 in comparison group 3 (p = .0181). Conclusion We showed the association of these microRNA-CNVs with CAD, T2DM or both simultaneously.

Noninvasive Serum Fibrosis Markers are Associated with Coronary Artery Calcification in Patients with Nonalcoholic Fatty Liver Disease.

Background/AimsAdvanced hepatic fibrosis is associated with cardiovascular disease (CVD) in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between noninvasive serum fibrosis markers and the coronary artery calcium score (CACS) in subjects with NAFLD.MethodsWe analyzed 665 NAFLD subjects without chronic liver disease or heart disease between 2011 and 2015. The noninvasive fibrosis markers that were used to evaluate the severity of hepatic fibrosis included the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) score, Forn’s index, and the aspartate aminotransferase to platelet ratio index (APRI).ResultsThe areas under the receiver operating characteristics curves for the NFS, FIB-4 score, Forn’s index and APRI for predicting CACS >100 were 0.689, 0.683, 0.659, and 0.595, respectively. According to the multivariate analysis, older age, increased body mass index (BMI), and decreased estimated glomerular filtration rate (eGFR) were significant factors associated with CACS >100. The NFS, FIB-4 score and APRI were significantly associated with CACS >100 after adjusting for age and gender (p=0.006, p=0.012, and p=0.012, respectively) and after adjusting for age, gender, BMI and eGFR (p=0.013, p=0.022, and p=0.027, respectively). Scores integrating noninvasive fibrosis markers and other risk factors improved the predictive accuracy.ConclusionsThe NFS and FIB-4 score were associated with coronary atherosclerosis in subjects with NAFLD. Furthermore, scores integrating these noninvasive scores and risk factors for CVD showed good discriminatory power in predicting CACS >100. Therefore, noninvasive serum fibrosis markers may be useful tools for identifying NAFLD subjects at a high risk for CVD.

Association of Lupus Nephritis With Coronary Artery Disease by ISN/RPS Classification: Results From a Large Real-world Lupus Population.

ObjectivePatients with systemic lupus erythematosus (SLE) are at an increased risk for developing coronary artery disease (CAD). Several studies suggest that the presence of lupus nephritis (LN) is independently associated with CAD. The purpose of our study was to assess whether the presence of LN is independently associated with CAD in our patient population and whether this association varies by class of LN.MethodsA retrospective cross‐sectional analysis was performed using medical records of patients 18 years and older with SLE at University of North Carolina Hospitals from April 4, 2014, to December 31, 2017. Subjects were identified using International Classification of Diseases, Ninth Revision (ICD‐9) and International Classification of Diseases, 10th Revision (ICD‐10) codes specific for SLE. LN class was defined by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. CAD was the outcome of interest. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsOur sample consisted of 3732 patients with SLE, of whom 598 (16%) had LN and 537 (14%) had CAD. When adjusting for demographics and factors associated with CAD and LN, the odds of having CAD were significantly higher for patients with SLE and LN compared with patients without LN (OR 1.47; 95% CI 1.07‐2.02; P = 0.017). Controlling for these factors, class III LN (OR 1.98; 95% CI 0.95‐4.12; P = 0.069) and class III/V LN (OR 2.23; 95% CI 1.09‐4.62; P = 0.028) were very strongly associated with CAD in subjects with LN compared with subjects without LN.ConclusionWe confirm the observations of previous studies that LN is significantly associated with CAD. Our study is the first to show the association between CAD and specific classes of LN.

Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease

Coronary artery disease (CAD) is a leading cause of death worldwide and frequently associated with mitochondrial dysfunction. Detailed understanding of abnormalities in mitochondrial function that occur in patients with CAD is lacking. We evaluated mitochondrial damage, energy production, and mitochondrial complex activity in human non-CAD and CAD hearts. Fresh and frozen human heart tissue was used. Cell lysate or mitochondria were isolated using standard techniques. Mitochondrial DNA (mtDNA), NAD + and ATP levels, and mitochondrial oxidative phosphorylation capacity were evaluated. Proteins critical to the regulation of mitochondrial metabolism and function were also evaluated in tissue lysates. PCR analysis revealed an increase in mtDNA lesions and the frequency of mitochondrial common deletion, both established markers for impaired mitochondrial integrity in CAD compared to non-CAD patient samples. NAD+ and ATP levels were significantly decreased in CAD subjects compared to Non-CAD (NAD+ fold change: non-CAD 1.00 ± 0.17 vs. CAD 0.32 ± 0.12* and ATP fold change: non-CAD 1.00 ± 0.294 vs. CAD 0.01 ± 0.001*; N = 15, P < 0.005). We observed decreased respiration control index in CAD tissue and decreased activity of complexes I, II, and III. Expression of ETC complex subunits and respirasome formation were increased; however, elevations in the de-active form of complex I were observed in CAD. We observed a corresponding increase in glycolytic flux, indicated by a rise in pyruvate kinase and lactate dehydrogenase activity, indicating a compensatory increase in glycolysis for cellular energetics. Together, these results indicate a shift in mitochondrial metabolism from oxidative phosphorylation to glycolysis in human hearts subjects with CAD.