Coronary Heart Disease Biomarkers Research Articles

Direct electrochemiluminescent immunosensing for an early indication of coronary heart disease using dual biomarkers

In this paper, a promising technology for obtaining an early indication and making a clinical diagnosis of coronary heart disease (CHD) is successfully designed. Specifically, label-free biosensors based on Au–Co nanoparticles (Au–Co NPs) were utilized to detect low-density lipoprotein (LDL) and oxidized low-density lipoprotein (ox-LDL), which are both CHD biomarkers. Conductive Au–Co NPs provided a prominent sensing platform and played the role of an efficient electrochemiluminescent (ECL) signaling amplifier. Conductive Au–Co NPs were fabricated using a simple method of water phase synthesis and were characterized using transmission electron microscope (TEM) and scanning electron microscope (SEM) images. An antibody was immobilized onto Au–Co NP-decorated indium tin oxide coated glass. After the formation of an immune complex between the antigen and antibody, using luminol as a sensing probe, it was found that the ECL signal was inhibited. Under the optimized conditions, the immunosensor exhibited sensitive detection of LDL over a wide linear range from 0.420 to 100 pg mL−1 with a detection limit of 0.256 pg mL−1. Likewise, a linear regression of the concentration of ox-LDL was obtained over the range from 0.500 pg mL−1 to 60.0 pg mL−1, with a detection limit of 0.330 pg mL−1. This research provides a new method for making a clinical diagnosis and obtaining an early indication of CHD due to the high performance sensing of these two biomarkers.

Discovering Novel Biochemical and Genetic Markers for Coronary Heart Disease in Qatari Individuals: The Initiative Qatar Cardiovascular Biorepository.

Background:We aimed to describe the creation and challenge of a DNA and plasma biorepository (Qatar Cardiovascular Biorepository) with linkage to the electronic health record of cardiovascular risk factors to facilitate discovery of novel genetic and proteomic biomarkers for coronary heart disease in Qatari individuals.Methods:A prospective case–control study was conducted between October 2013 and February 2018. CHD was defined as a history of an acute coronary syndrome (myocardial infarction [MI]/unstable angina) or coronary revascularization. Controls were identified from blood donors who had no history of coronary heart diesase. After informed consent, blood samples were obtained for DNA and plasma. Demographic, laboratory, and clinical variables were derived from the electronic medical record, and information regarding history of cardiovascular diseases and risk factors was collected from surveys. Challenges in establishing the biorepository were noted, and processes to promote use of the biorepository by Qatari investigators were put in place.Results:During the study period, 2671 individuals were approached; of them, 2087 participants were recruited (1029 patients and 1058 controls). Relevant risk factors were ascertained from the electronic health record and surveys. The mean age was 49 ± 16 years, with 61% males. Challenges included setting up the infrastructure for qatar cardiovascular biorepository, developing an informed consent document in Arabic/English, and meeting target recruitment goals. The prevalence of diabetes mellitus, hypertension, dyslipidemia, and smoking was 41%, 44.5%, 40%, and 19%, respectively. History of myocardial infarction, percutaneous coronary intervention, and coronary artery bypass surgery was 55%, 68%, and 17%, respectively, among patients.Conclusions:This study addresses the challenges in setting up qatar cardiovascular biorepository, the first cardiovascular genomics biorepository in the Arab Middle Eastern region. QCBio is a unique resource for identifying genetic susceptibility variants and novel circulating markers for coronary heart disease in Qatari adults and enables individualized assessment of risk for coronary heart disease.

Relationship between Platelet Indices and Coronary Heart Disease in Malaysian Population

Coronary Heart Disease (CHD) is a major cause of mortality worldwide and in Malaysia. Early screening and diagnosis reduce the mortality rate of this disease by 15%-30%. CHD is caused by atherosclerosis and platelets have been found to play a major role in the development of atherosclerotic lesions. Although other biomarkers exist for CHD, platelet indices can be detected earlier and are routinely available. Hence this project was undertaken to study the relationship between platelet indices and CHD, as well as to find the diagnostic significance of platelet indices by comparing with other inflammatory biomarkers of CHD. This is a case control study carried out from July 2019 to September 2019, at the National Heart Institute, Kuala Lumpur, Malaysia. The study population consisted of 100 normal control subjects and 100 case study subjects. Once eligibility was confirmed, patient data was filled in the case study forms, while the observational laboratory data consisting of platelet indices, were collected from the Sysmex XN-1000 analyser. Statistical analysis was then carried out using the SPSS 16.0 Software, whereby an independent sample ttest was done and a p-value of less than 0.05 was considered statistically significant. Results showed that the levels of PDW, MPV and P-LCR were increased significantly (p-value less than 0.05) in CHD patients, while the levels of PC and PCT between the two groups showed no statistically significant difference. Nevertheless, it was found that these elevations could also be due to other risk factors, such as gender, smoking, Diabetes Mellitus, and hypertension. Hence, further research should be carried out to study the potential mechanisms behind the increase of platelet indices levels as a result of CHD alone, as it has the potential to be a beneficial risk predicting factor for CHD.

MicroRNA-451b Participates in Coronary Heart Disease By Targeting VEGFA.

Coronary artery disease (CAD) is one of the main causes of hospitalization worldwide and has high morbidity. MicroRNAs (miRNAs) play an important role in the pathogenesis of cardiovascular diseases. miR-451 is a special miRNA that is involved in many cancers’ development. At present, there is no research about miR-451 in coronary heart disease. In this study, we aimed to identify the action mechanism of miR-451 in coronary heart disease and human umbilical vein endothelial cells (HUVECs). In this study, we found that miR-451 is up-regulated in the peripheral blood of patients with coronary heart disease. Moreover, TargetScan and dual-luciferase reporter gene assay results showed that VEGFA is a direct target gene of miR-451. C (CCK-8) and flow cytometry assay results showed that miR-451 mimic significantly inhibits cell proliferation and promotes apoptosis in HUVECs. Moreover, we found that the role of miR-451 in HUVECs is associated with the PI3K-Akt-mTOR pathway. Taken together, the data indicates that miR-451 might be a novel bio-marker for coronary heart disease.

Possible Use of Blood Tryptophan Metabolites as Biomarkers for Coronary Heart Disease in Sudden Unexpected Death.

Coronary heart disease (CHD) is the major cause of death in sudden unexpected death (SUD) cases. Tryptophan (TRP) and its metabolites are correlated with the CHD patient but less studies in the SUD. The aim of this study was to evaluate the relationship of TRP and its metabolites with the CHD in the SUD cases. Blood samples and heart tissues were collected from CHD subjects (n = 31) and the control group (n = 72). Levels of kynurenine (KYN), kynurenic acid (KYA), xanthurenic acid (XAN), 3-hydroxyanthranillic acid (HAA), quinolinic acid (QA), picolinic acid (PA) and 5-hydroxyindoleacetic acid (HIAA) were determined by HPLC-DAD. A severity of heart occlusion was categorized into four groups, and the relationship was measured with the TRP metabolites. The HIAA and The KYN levels significantly differed (p < 0.01) between the CHD group and the control group. Lower levels of QA/XAN, PA/KA, HAA/XAN, KYN/XAN and KYN/TRP were found in the CHD group. However, PA/HAA, PA/HIAA, PA/KYN and XAN/KA values in the CHD group were higher than the control group (p < 0.05). This study revealed that the values of PA/KA and PA/HAA provided better choices for a CHD biomarker in postmortem bodies.

Epigenetic modulation of glycoprotein VI gene expression by DNA methylation

AimsGlycoprotein VI (GPVI) is an important platelet membrane receptor. The expression of GPVI on platelet membranes is increased in patients with coronary heart disease (CHD). DNA methylation is one of the most common post-replication and pre-transcriptional modifications and plays a critical role in the regulation of gene expression. Here, we aimed to reveal how methylation regulates GPVI expression. Main methodsPyrosequencing was used to determine whether the GPVI promoter region in leukocytes from CHD patients is hypomethylated. The expressions of GPVI in CHD patients were detected using qRT-PCR and Western blot. The effect of methylation of the GPVI promoter region on regulating its transcriptional activity was analyzed using in vitro luciferase assay. The expression of P-selectin in platelet-like particles was determined using flow cytometry, and SYK phosphorylation was observed using Western blot. Key findingsWe found that the GPVI promoter region in leukocytes from CHD patients was hypomethylated and the expression of GPVI at the mRNA and protein level was elevated in CHD patients. We also found that the hypermethylation of GPVI promoter region inhibited the expression of GPVI in the −322 to +75, −539 to +75, and −937 to +75 regions in Dami cells. Moreover, the data showed that the methylation or demethylation regulated the GPVI expression and platelet-like particle activation in Dami cells. SignificanceTaken together, these results indicate that DNA methylation regulates GPVI expression and that CpG methylation levels in the promoter region of the GPVI gene may be a biomarker of CHD.

Circulating miR-30c as a predictive biomarker of type 2 diabetes mellitus with coronary heart disease by regulating PAI-1/VN interactions

AimsType 2 diabetes mellitus (DM2) is associated with coronary heart disease (CHD) and is characterized by high levels of plasminogen activator inhibitor (PAI)-1. Circulating microRNAs have been reported as potential diagnostic biomarkers for DM2 and CHD. However, the underlying mechanisms have largely remained unclear. Main methodsThe changes of circulating miR-30c, PAI-1 and vitronetin (VN) in plasma from CHD, noncomplicated (NC) + DM2, CHD + DM2 subjects and control individuals were assessed by quantitative reverse transcription PCR (qRT-PCR) and ELISA assays, respectively. The effects of miR-30c on VN expression by targeting PAI-1 were assessed in vitro SMC and in ex vivo plasma, using bioinformatic analysis, miRNA transfection, luciferase assays, qRT-PCR and western blot, respectively. Key findingsWe found that decreased circulating miR-30c was negatively correlated with the severity of coronary lesions and the resulting elevated PAI-1 and VN levels. Circulating miR-30c significantly distinguished between patients with CHD + DM2, NC + DM2, CHD and control subjects, and that were significantly associated with certain risk factors for progression from a normal individual to one with CHD + DM2. Furthermore, we also showed that miR-30c plays a previously unrecognized role in regulating the expression of VN levels via regulating PAI-1 levels in vitro SMC and in ex vivo plasma. SignificanceThese findings provide a novel regulatory mechanism of miR-30c in regulating PAI-1/VN interactions and that may serve as a diagnostic biomarker of DM2 that is complicated with CHD.

Usefulness of Certain Protein Biomarkers for Prediction of Coronary Heart Disease

Identification of biomarkers can help monitor and prevent cardiovascular disease (CVD) risk. We performed an exploratory analysis to identify potential biomarkers for coronary heart disease (CHD) in participants from the Life Conditions, Stress, and Health study. A total of 1,007 participants (50% women), randomly selected from the general population, were followed for incident CHD at 8 and 13 years of follow-up. Plasma levels of 184 CVD-related biomarkers were measured in samples collected at baseline in 86 cases with CHD and 184 age- and sex-matched controls by proximity extension assay. Biomarker levels were presented as normalized protein expression values (log 2 scale). After adjusting for confounding factors, 6 biomarkers showed significant association with incident CHD at 13 years. In a sensitivity analysis, this association remained significant at 8 years for 3 biomarkers; collagen α-1(I) chain (COL1A1), bone morphogenetic protein-6 (BMP-6), and interleukin-6 receptor α chain (IL-6Rα). When entering these biomarkers in the full adjustment model simultaneously, their association with incident CHD at 13 years remained significant, hazards ratio being 0.671, 0.335, and 2.854, respectively per unit increase in normalized protein expression values. Subjects with low COL1A1, low BMP-6, and high IL-6Rα levels had a hazards ratio of 5.097 for incident CHD risk (p = 0.019), compared with those without. In conclusion, we identified COL1A1, BMP-6 and IL-6Rα as biomarkers for incident CHD over a long-term follow-up in this exploratory analysis. For COL1A1 and BMP-6 this has not been previously reported. Further studies are needed to confirm our findings and establish their clinical relevance.

Identification and Validation of Plasma Metabolomics Reveal Potential Biomarkers for Coronary Heart Disease.

Coronary heart disease (CHD) is a prevalent and chronic life-threatening disease. However, there is no reliable way for early diagnosis and prevention of CHD so far. The precise molecular pathological mechanism of CHD remains obscure. Therefore, developing novel biomarkers is urgently needed.In order to evaluate the potential of untargeted plasma metabolomics in biomarker discovery for characterizing CHD, plasma metabolites from patients newly diagnosed with CHD and controls were profiled using liquid chromatography quadrupole time-of-flight mass spectrometry. Differential metabolites were identified using both univariate and multivariate statistical analyses. Metabolites with significant changes were subjected to binary logistic regression analysis, and a CHD prediction model was established. A total of 28 differential plasma metabolites were identified, of which the concentrations of 11 increased significantly and those of 17 decreased significantly in patients with CHD compared with controls. The altered metabolic pathways included reduced phospholipid metabolism, increased monoglyceride metabolism, and abnormal fatty acid metabolism. Furthermore, binary logistic regression showed that nine metabolites could be used as potential plasma biomarkers for the diagnosis of CHD. The prediction model based on these nine metabolites was then tested with an independent cohort of samples (area under the curve = 0.929).Our plasma metabolomics study not only yielded fundamental insights into dysregulated metabolism in CHD but also presented a combinatorial biomarker that might support the clinical diagnosis of CHD.

Cholesterol efflux capacity, HDL cholesterol, and risk of coronary heart disease: a nested case-control study in men

The capacity of HDLs to accept cholesterol effluxing from macrophages has been proposed as a new biomarker of HDLs' anti-atherogenic function. Whether cholesterol efflux capacity (CEC) is independent of HDL cholesterol (HDL-C) as a biomarker for coronary heart disease (CHD) risk in a generally healthy primary-prevention population remains unanswered. Therefore, in this nested case-control study, we simultaneously assessed CEC (using J774 cells) and plasma HDL-C levels as predictors of CHD in healthy middle-aged and older men not receiving treatment affecting blood lipid concentrations. We used risk-set sampling of participants free of disease at baseline from the Health Professionals Follow-Up Study, and matched cases (n = 701) to controls 1:1 for age, smoking, and blood sampling date. We applied conditional logistic regression models to calculate the multivariable relative risk and 95% CIs of CHD over 16 years of follow-up. CEC and HDL-C were correlated (r = 0.50, P < 0.0001). The risk (95% CI) of CHD per one SD higher CEC was 0.82 (0.71-0.96), but completely attenuated to 1.08 (0.85-1.37) with HDL-C in the model. The association per one SD between HDL-C and CHD (0.66; 0.58-0.76) was essentially unchanged (0.68; 0.53-0.88) after adjustment for CEC. These findings indicate that CEC's ability to predict CHD may not be independent of HDL-C in a cohort of generally healthy men.

Identification of coronary heart disease biomarkers with different severities of coronary stenosis in human urine using non-targeted metabolomics based on UPLC-Q-TOF/MS

BackgroundCoronary heart disease (CHD) is the leading cause of death worldwide, and its pathogenesis has attracted much attention. Metabolomics serves as an important tool for diagnosing diseases and exploring their pathogenesis in recent years. In this study, CHD patients were studied by comparing them with normal subjects to elucidate biomarkers that are linearly correlated with the severity of coronary stenosis. MethodsAn ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze the urine metabolites of CHD patients and normal subjects. A total of 131 subjects included 27 patients who presented with 50–69% coronary stenosis, 22 with 70–89% stenosis, 29 with 90–99% stenosis, 24 with 100% stenosis, and 29 normal subjects. ResultsA total of 14 potential biomarkers associated with CHD were identified, and among them 4 biomarkers were linearly correlated with the severity of coronary stenosis in CHD patients. The metabolic pathways involved were amino acid metabolism, fatty acid metabolism, energy metabolism, and other pathways. ConclusionThis study identified the biomarkers and metabolic pathways that may be involved in the occurrence and development of CHD, laying a theoretical foundation for better diagnosis and treatment of CHD in the future.

MiR-17 regulates the proliferation and apoptosis of endothelial cells in coronary heart disease via targeting insulin-like-growth factor 1

Coronary heart disease (CHD) is one of the main risks of death, which is mainly caused by coronary arteries arteriosclerosis. The present study aims to investigate the potential roles of miR-17 in CHD. In the present study, Human umbilical vascular endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL). qRT-PCR and western blot were used to examine the mRNA and protein levels, respectively. CCK-8 and flow cytomtry were conducted to determine the proliferation and apoptosis of ox-LDL treated HUVECs. Moreover, luciferase assay was performed to confirm whether insulin-like Growth Factor-1 (IGF-1) was a target of miR-17. The results showed that miR-17 was upregulated in ox-LDL treated HUVECs, while IGF-1 was downregulated. The luciferase activity of ox-LDL treated HUVECs was decreased after the treatment of miR-17 mimics and IGF-1 3’UTR WT. Moreover, overexpressed miR-17 promoted the cell viability and inhibited the apoptosis of ox-LDL treated HUVECs, which was more potent after the treatment of IGF-1 siRNA. Furthermore, the expression of Bax and Caspase3 was decreased, and Bcl-2 was increased in ox-LDL treated HUVECs transfected with miR-17 mimics, which was further decreased after transfection with IGF-1 siRNA. Taken together, miR-17 may regulate the proliferation and apoptosis of ox-LDL treated HUVECs. miR-17 may be a promising biomarker for CHD.

Anti-inflammatory and antioxidative effects of Dan-Lou tablets in the treatment of coronary heart disease revealed by metabolomics integrated with molecular mechanism studies

Ethnopharmacological evidenceThe Dan-Lou tablet (DLT), a well-known Chinese prescription, has definitive clinical efficacy in the treatment of precordial discomfort and pain caused by coronary heart disease (CHD). However, the pharmacological mechanism of DLT in the treatment of CHD has not been clearly elucidated and needs to be further explored. Aim of the studyWe aimed to identify relevant biological pathways by assessing changes in biomarkers in response to DLT intervention in CHD to reveal the potential biological mechanism of DLT treatment for CHD. Materials and methodsThe major chemical components in DLT were qualitatively analyzed using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and a model of CHD in rats was subsequently established with a high-fat diet and left anterior coronary artery ligation (LADCA) followed by DLT intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after DLT administration were measured by PLS-DA, and two pathways of DLT treatment for CHD were predicted. Finally, predicted metabolomic pathways were verified by detecting and analyzing tissues from the rat model, revealing the mechanism of DLT in the treatment of CHD. ResultsForty-five major chemical components were identified by the chemical characterization of DLT. In terms of metabolism, 17 biomarkers of CHD in rats were identified. Among these biomarkers, linoleic acid, γ-linolenic acid and lysophosphatidylcholines (LPCs) were found to play an important role in energy metabolism and glycerophospholipid metabolism. Protein analysis revealed that EGFR phosphorylation was inhibited in CHD rats after DLT treatment, which lowered the expression of TNF-α, IL-6 and MMP9, decreased the expression levels of ox-LDL and MDA, and increased the expression of SOD. ConclusionThe mechanism of DLT in the treatment of CHD involves inhibiting the expression of EGFR and the activation of the MAPK signaling pathway by regulating glycerophospholipid metabolism (LPCs) and energy metabolism (linoleic acid and γ-linolenic acid). Therefore, inflammation-related (TNF-α, IL-6, MMP9) and oxidative stress-related (ox-LDL, MDA, SOD) indicators are affected, leading to the regulation of the oxidative stress state and anti-inflammatory effects.

Exploring potential biomarkers of coronary heart disease treated by Jing Zhi Guan Xin Pian using high-throughput metabolomics.

Coronary heart disease (CHD) is a relatively complex disease characterized by narrowing of the arterial lumen and reduction of blood flow to the heart. There is no effective early diagnosis and prevention method. Jing Zhi Guan Xin Pian (JZGXP) is a new preparation prepared from the effective extract of Guanxin II. It is made of five components of traditional Chinese medicine and functions by promoting blood circulation and removing blood stasis and is used for the treatment of CHD and angina pectoris. In our study, a CHD rat model was prepared using a high-fat diet combined with intraperitoneal injection of vitamin D3. Clinical biochemical indexes (TG, CHO and HDL-C), histopathology (coronary and myocardial tissue), electrocardiogram and cardiac indexes were used to evaluate the efficacy of JZGXP in the treatment of CHD model rats. UPLC-HDMS-based metabolomics techniques were used to find metabolic profiles, biomarkers and related metabolic pathways in CHD models and to evaluate the effects of JZGXP on them. At the same time, the targets of JZGXP for the treatment of CHD were analyzed. Our study ultimately identified 25 biomarkers associated with CHD models. Further studies found that these 25 biomarkers involved 9 metabolic pathways in the body and found that JZGXP can recall 21 biomarkers in the urine of model rats and these biomarkers involve nine metabolic pathways. Finally, the targets of JZGXP for the treatment of CHD were β-alanine metabolism and tyrosine metabolism, i.e. amino acids metabolism. This study showed that metabolomics technology is effective for exploring potential biomarkers associated with syndromes or diseases and the therapeutic mechanisms of a traditional Chinese medicine formulation.

Hearing loss is associated with increased CHD risk and unfavorable CHD-related biomarkers in the Dongfeng-Tongji cohort

Background and aimsThe association between hearing loss and coronary heart disease (CHD) is inconsistent. We aimed to investigate the association of hearing loss with prevalent CHD and CHD-related biomarkers among a middle aged and elderly Chinese population. MethodsWe included 14,755 Chinese aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate or greater levels by the pure tone average (PTA) at low frequency and high frequency, respectively. Logistic regression models were used to estimate the odds ratios (ORs) of CHD risk in relation to hearing loss. Linear regression models were used to evaluate the effect of hearing loss on CHD-related biomarkers. ResultsThe adjusted ORs for prevalent CHD increased gradually with the increasing hearing loss levels. Compared with normal hearing, individuals having mild- and moderate or greater-hearing loss had a higher CHD risk of 19% and 20% at low frequency, and 33% and 41% at high frequency, respectively (all p for trend < 0.05). The associations were more evident among subjects who were females, overweight, exposed to occupational noise and with hyperglycemia, hypertension or dyslipidemia at low frequency, and those with hyperglycemia at high frequency. Meanwhile, moderate or greater hearing loss combined with overweight, hyperglycemia, hypertension or dyslipidemia had joint effects on CHD. In addition, the majority of CHD-related biomarkers worsened with increasing hearing loss levels. ConclusionsThere may be a dose-response relationship between hearing loss and CHD prevalence, and the association could partially be explained by intermediate CHD-related biomarkers.

The SNP rs10911021 is associated with oxidative stress in coronary heart disease patients from Pakistan

Backgroundrs10911021 (a single nucleotide polymorphism present upstream of the GLUL gene) affects glutamic acid metabolism, and was shown to be associated with coronary heart disease (CHD) in patients with T2DM but a definite mechanism is unknown. It may affect glutathione cycle, an important effector in the antioxidant defense mechanism, in the cells. We checked the association of this SNP with CHD and oxidative stress biomarkers, malondialdeheyde (MDA), GSH and GSSG in Pakistani patients.MethodsA total of 650 subjects (425 CHD cases and 225 controls) were genotyped by TaqMan allelic discrimination technique. The levels of MDA, GSH and GSSG were measured by standard protocols.ResultsThe risk allele frequency was higher in cases than controls, but the difference was insignificant (p = 0.55). The SNP was not associated with CHD (p = 0.053) but when the analysis was limited to CHD patients having DM, a significant association (p = 0.03) was observed. The blood levels of MDA and GSSG were higher while that of GSH was significantly lower in the cases than the controls (p < 0.05). Each risk allele increased MDA and GSSG by 0.29 (0.036) mmol/l and 0.4 (0.04) mmol/l, respectively, while decreased GSH by −0.36 (0.03) mmol/l. The SNP was not associated with any of the tested blood lipids.ConclusionThe SNP rs10911021 was associated with CHD only in patients having diabetes, but the SNP was associated with total oxidative stress biomarkers MDA and GSH and GSSG levels. As the SNP rs10911021 showed significant association with oxidative stress parameters and these parameters should an increased oxidative stress in the CHD subjects, it can be concluded that the SNP may have contributed to increase the risk of heart diseases in the diabetic subjects by increasing the oxidative stress.

Circulating MiR-146a May be a Potential Biomarker of Coronary Heart Disease in Patients with Subclinical Hypothyroidism

Background/Aims: Subclinical hypothyroidism (SCH) plays a crucial role in the development and progression of coronary heart disease (CHD). However, any associated changes in the circulating microRNAs (miRNAs) levels and slightly elevated thyroid stimulating hormone (TSH) levels in CHD patients are unknown. miR-146a is a well known miRNA associated with inflammatory autoimmune diseases. Here, we evaluated miR-146a expression in patients, with the goal of re-evaluating the effect of SCH on CHD. Methods: A total of 192 study subjects who underwent coronary angiography for either suspected or confirmed CHD were enrolled in 3 groups: CHD with SCH, CHD alone, and healthy controls. The circulating levels of miR-146a were quantified using qRT-PCR. Results: Levels of miR-146a were positively correlated with CHD severity, as indicated by the Gensini score (r=0.354). The relative expression of miR-146a in the CHD+SCH, CHD and healthy control groups was 2.223±0.827, 1.588±0.726 and 0.632±0.309, respectively. Plasma TSH levels were positively correlated with miR-146a levels (r=0.321). According to multivariate logistic regression analyses, miR-146a levels were associated with the incidence of CHD in patients with SCH. For diagnosing CHD, the area under the ROC curve (AUC) of miR-146a and TSH was 0.779 and 0.752, respectively. When the TSH and miR-146a levels were combined to form a composite panel, the AUC of the panel was 0.858. Conclusion: Plasma miR-146a levels correlated with the severity of coronary atherosclerosis and increased with TSH slightly elevated in patients with CHD. Thus, miR-146a may have good predictive value for CHD among individuals with elevated TSH levels.

Inflammatory biomarkers of coronary heart disease.

Coronary heart disease (CHD) is one of the leading causes of death worldwide. CHD is characterized by formation of arterial plaques which are mainly comprised of lipids, calcium and inflammatory cells. These plaques narrow the lumen of coronary arteries leading to episodic or persistent angina. Rupture of these plaques leads to the formation of thrombus, which as a result of cessation of blood flow, causes myocardial infarct and death. CHD is exacerbated by risk factors including obesity, diabetes mellitus, and hypertension. Diagnosis is established by the level of blood cholesterol, triglycerides and lipoproteins Inflammation is considered significant in the pathogenesis of CHD and for this reason, severity and prognosis of CHD is assessed by the levels of inflammatory biomarkers, including interleukin-6, C-reactive protein (CRP), complement, CD40 and myeloperoxidase (MPO).

Association of Coronary Artery Calcification with Estimated Coronary Heart Disease Risk from Prediction Models in a Community-Based Sample of Japanese Men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

Aim: The clinical significance of coronary artery calcification (CAC) is not fully determined in general East Asian populations where background coronary heart disease (CHD) is less common than in USA/Western countries. We cross-sectionally assessed the association between CAC and estimated CHD risk as well as each major risk factor in general Japanese men.Methods: Participants were 996 randomly selected Japanese men aged 40–79 y, free of stroke, myocardial infarction, or revascularization. We examined an independent relationship between each risk factor used in prediction models and CAC score ≥ 100 by logistic regression. We then divided the participants into quintiles of estimated CHD risk per prediction model to calculate odds ratio of having CAC score ≥ 100. Receiver operating characteristic curve and c-index were used to examine discriminative ability of prevalent CAC for each prediction model.Results: Age, smoking status, and systolic blood pressure were significantly associated with CAC score ≥ 100 in the multivariable analysis. The odds of having CAC score ≥ 100 were higher for those in higher quintiles in all prediction models (p-values for trend across quintiles < 0.0001 for all models). All prediction models showed fair and similar discriminative abilities to detect CAC score ≥ 100, with similar c-statistics (around 0.70).Conclusions: In a community-based sample of Japanese men free of CHD and stroke, CAC score ≥ 100 was significantly associated with higher estimated CHD risk by prediction models. This finding supports the potential utility of CAC as a biomarker for CHD in a general Japanese male population.

Hepatocyte growth factor demonstrates racial heterogeneity as a biomarker for coronary heart disease

ObjectiveTo determine if hepatocyte growth factor (HGF), a promising biomarker of coronary heart disease (CHD) given its release into circulation in response to endothelial damage, is associated with subclinical and...