Project description:BackgroundAK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications.MethodsA total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student's t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman's correlation.ResultsAK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501-0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528-0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006).ConclusionAK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.
Project description:BackgroundThe relationship between galectin-3 (Gal-3) and coronary artery disease (CAD) has not been fully elucidated.AimThis study aimed to determine the relationship between the presence and severity of CAD and serum Gal-3 levels.Patients and methodsThree-hundred thirty-one consecutive CAD patients were enrolled as the study group. An additional 62 patients without CAD were enrolled as the control group. Serum Gal-3 levels were separately compared between the non-CAD and CAD groups, among the stable CAD and Acute coronary syndrome (ACS) groups, and between CAD patients with low and high SYNTAX scores (SSs). The 1-year cumulative rate of major adverse cardiac events (MACEs) was also compared among ACS patients by Gal-3 levels.ResultsSerum Gal-3 was significantly higher in the CAD group than in the non-CAD group 3.89 (0.16-63.67) vs. 2.07 (0.23-9.38) ng/ml, P < 0.001. Furthermore, serum Gal-3 was significantly higher in the non-ST-segment elevation ACS (NSTE-ACS) group than that in the stable CAD group, 4.72 (1.0-16.14) vs. 2.23 (0.65-23.8) ng/ml, P = 0.04 and higher in the ST-segment elevation myocardial infarction (STEMI) group than that in the stable CAD group 7.87 (0.59-63.67) vs. 2.23 (0.65-23.8) ng/ml, P < 0.001. Serum Gal-3 level was an independent predictor of ACS compared with stable CAD group (OR = 1.131, 95% CI: 1.051-1.217, P = 0.001) as well as high SS (OR = 1.030, 95% CI: 1.021-1.047, P = 0.038) after adjust other confounding risk factors. Acute coronary syndrome patients with Gal-3 levels above the median (gal-3 = 4.78 ng/ml) showed a higher cumulative MACE rate than those with Gal-3 levels below the median. After adjusting other confounding risk factors, Gal-3 remained an independent risk factor for the cumulative rate of MACEs in ACS patients (6% higher rate of MACEs incidence per 1 ng/ml increment of Gal-3).ConclusionGalectin-3 correlated with the presence of CAD as well as coronary stability and complexity. Galectin-3 may be valuable in predicting mid-term prognosis in ACS patients.
Project description:BackgroundHypertension is one of the major risk factors for cardiovascular events. This study aims to analyse the association of endothelial function and limb artery indices with coronary artery stenosis (CAS) severity in hypertension based on easily accessible and detailed clinical information, and to help accurately identify high-risk groups and avoid missed diagnosis and misdiagnosis.MethodsAdmission data of 1,375 consecutive hypertensive patients complicated with suspected coronary atherosclerotic heart disease (CHD) from September 2020 to August 2021 in China-Japan Friendship Hospital were retrospectively assessed. All candidates underwent coronary angiography for screening. A total of 600 eligible patients were classified in the CHD group (n = 359) and non-CHD group (n = 241) based on their coronary angiography results. Subjects in the CHD group were further assigned to 'high stenosis' (n = 178) and 'low stenosis' (n = 181) subgroups based on the median value of Gensini score. Endothelial function and limb artery indicators, including brachial artery flow-mediated vasodilatation (FMD), ankle-brachial index (ABI) and brachial-ankle pulse velocity (baPWV), were examined and compared between subgroups. Multivariate logistic regression analysis and multiple linear regression analysis were carried out to select independent risk factors of CAS severity in hypertension. A predictive equation was conducted according to the results of multivariate logistic regression analysis to make clinical practice easier. As the receiver operating characteristic (ROC) curve had been plotted, the predictive ability of endothelial function and limb artery indicators in CAS severity in hypertension was detected by the area under the curve (AUC).ResultsIn patients with hypertension, the FMD (p = 0.023), ABI (p < 0.001) and baPWV (p < 0.001) of CHD patients appeared substantially different from the non-CHD patients. Furthermore, the ABI (p < 0.001) and baPWV (p = 0.032) both independently associated with CAS severity in hypertensive patients with CHD. Based on the results of multivariate logistic regression analysis with CAS severity as a dependent variable, a predictive equation of baPWV, ABI and FMD was developed: combined coefficient = Logit(p)=5.531-0.218*FMD-7.019*ABI + 0.244*baPWV. From the combined coefficients of baPWV, ABI and FMD, the largest AUC was 0.800, suggesting a powerful predictive value of CAS severity in hypertensive patients, followed by ABI (AUC = 0.747, 95%CI 0.693-0.796), baPWV (AUC = 0.704, 95%CI 0.648-0.756) and FMD (AUC = 0.588, 95%CI 0.529-0.645).ConclusionThis study shows that baPWV, ABI and FMD are independent risk factors for CHD, of which, baPWV and ABI are strongly associated with CAS severity in hypertensive patients. The predictive ability of CHD in hypertensive patients may be enhanced through combining the three endothelial function and limb artery indicators. The results may help to facilitate clinical decision-making during treatment and management of coronary artery disease.
Project description:Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AS) are the heart diseases accounting for the highest proportion of cardiac surgeries. Routine biomarkers for an earl detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis and to evaluate their severity with imaging techniques before they become advanced to the point where intervention or surgery have limited therapeutic benefit. Urine is an attractive biofluid for biomarker assessment, provided the noninvasive nature of its collection. Therefore, we conducted a shotgun proteomics analysis of urine collected from 12 CAD and/or AS patients and 11 cardiovascular disease-free controls, aiming at identification of putative molecular candidates that could differentiate these diseases from healthy subjects
Project description:Coronary artery disease (CAD) is one of the most important cardiovascular diseases. Lifestyle and genetic factors play important roles in the development of CAD. The aim of the study is to examine the interaction of dietary patterns and genes on the likelihood of abnormal lipid profile and coronary artery stenosis in Iranians undergoing coronary angiography. This cross-sectional study was performed on 440 patients who underwent coronary angiography. The factor analysis method was used to extract dietary patterns. Commercial kits have been used to assess biochemical parameters. The detection of the rs28362491 genotype was carried out by the method of restriction fragment length polymorphism. Traditional (TDP) and western dietary pattern (WDP) were extracted. We observed an interaction of adherence to TDP and rs28362491 on the odds of having a high Gensini score. These interactions indicated that higher adherence to TDP was associated with higher odds of having a high Gensini score for patients with DD genotype than for those with II genotype. (OR 2.33, 95%CI 1.00-5.44; P = 0.05). These interactions remained statistically significant even after confounder variables. We observed an interaction between higher adherence to TDP and rs28362491 variants on the odds of high low-density lipoprotein cholesterol levels (P = 0.04) in the unadjusted model. We found a significant interaction of this polymorphism and higher adherence to WDP on the odds of having a high Gensini score in the unadjusted model (P = 0.04). This study provides a basis for future research on NF-KB1 gene and diet interaction. More large-scale longitudinal studies are needed to validate these findings.
Project description:PurposeAn important aspect in the prevention and treatment of coronary artery disease is the functional evaluation of narrowed blood vessels. Medical image-based Computational Fluid Dynamic methods are currently increasingly being used in the clinical setting for flow studies of cardio vascular system. The aim of our study was to confirm the feasibility and functionality of a non-invasive computational method providing information about hemodynamic significance of coronary stenosis.MethodsA comparative method was used to simulate the flow energy losses in real (stenotic) and reconstructed models without (reference) stenosis of the coronary arteries under stress test conditions, i.e. for maximum blood flow and minimal, constant vascular resistance. In addition to the absolute pressure drop in the stenotic arteries (FFRsten) and in the reconstructed arteries (FFRrec), a new energy flow reference index (EFR) was also defined, which expresses the total pressure changes caused by stenosis in relation to the pressure changes in normal coronary arteries, which also allows a separate assessment of the haemodynamic significance of the atherosclerotic lesion itself. The article presents the results obtained from flow simulations in coronary arteries, reconstructed on the basis of 3D segmentation of cardiac CT images of 25 patients from retrospective data collection, with different degrees of stenoses and different areas of their occurrence.ResultsThe greater the degree of narrowing of the vessel, the greater drop of flow energy. Each parameter introduces an additional diagnostic value. In contrast to FFRsten, the EFR indices that are calculated on the basis of a comparison of stenosed and reconstructed models, are associated directly with localization, shape and geometry of stenosis only. Both FFRsten and EFR showed very significant positive correlation (P < 0.0001) with coronary CT angiography-derived FFR, with a correlation coefficient of 0.8805 and 0.9011 respectively.ConclusionThe study presented promising results of non-invasive, comparative test to support of prevention of coronary disease and functional evaluation of stenosed vessels.
Project description:BackgroundCoronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). Some studies reported the ceramide species are associated with the ACS and major adverse cardia and cerebrovascular events (MACE). However, few studies investigated the association between plasma ceramide levels and the severity of stenosis, together with the onset of diseases. This aim of the present study was to investigate the association betweencertain ceramide species, coronary artery stenosis and acute coronary syndrome.MethodsFive hundred fifty-three patients with definite or suspected CAD were recruited and received angiography. Subjects were assigned into 4 groups according to the severity of coronary artery stenosis. The measurements of 4 plasma ceramide species, namely, Cer (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), Cer (d18:1/24:0) were carried out by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the ratio of Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) to Cer (18:1/24:0), respectively, were calculated as index to evaluate the association between plasma ceramides levels and coronary artery stenosis. Multiple logistic regression analysis was used to establish the prognostic model for the prediction of ACS risk.ResultsAfter the adjustment by multiple clinical risk factors including age, gender, pre-existing myocardial/cerebral infarction, hemoglobin A1c% (HbA1c%), smoking and the diagnosis during index hospitalization, multiple logistic regression analysis showed that the high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c%, unstable angina (UAP) and acute myocardial infarction (AMI) diagnosis (compared with atherosclerosis) during index hospitalization were associated with more severe coronary artery stenosis. Furthermore, the prognostic model was established after adjustment of risk factors and the area under curve (AUC) of receiver operating characteristics (ROC) for the prognostic model was 0.732 and 95% CI was 0.642-0.822.ConclusionThe severity of coronary artery stenosis is associated with high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c% and AMI. Although the reported prognostic model showed a good discrimination, further investigation on long term MACE is needed to evaluate the role of ceramide for the prediction of MACE risk.
Project description:ObjectiveTo investigate the association of CXCL12 and CXCR4 polymorphisms with the genetic risk and severity of coronary stenosis in patients with coronary artery disease (CAD).MethodsCompetitive allele specific PCR(KASP) was performed to identify the genotypes of rs2297630 and rs2322864 polymorphisms in 302 CAD patients and 302 age-and gender-matched healthy controls. The severity of CAD patients was assessed by the Gensini scoring system according to the results of coronary arteriography. The association of rs2297630 and rs2322864 polymorphisms with genetic risk of CAD and Gensini scores were analyzed by unconditional logistic regression and multivariate linear regression respectively.ResultsThere were significant differences in the genotype and allele frequencies of both rs2297630 and rs2322864 between the CAD group and healthy control (all P<0.01). Regression analysis showed that rs2297630 polymorphism was associated with genetic risk of CAD and Gensini scores (all P<0.01). People who carried the AA genotype suffered higher risk of CAD susceptibility and more serious coronary stenosis (all P<0.01), compared with GG genotype carriers. There was also significant association between rs2322864 polymorphism and genetic risk of CAD (P<0.01); those who carried the CT genotype had higher risk of CAD (P<0.01), compared with TT genotype carriers. However, rs2322864 polymorphism was not associated with the severity of coronary stenosis (P>0.05).ConclusionsGene polymorphism of CXCL12 rs2297630 is associated with the genetic risk of CAD and the severity of coronary stenosis. Moreover, the gene polymorphism of CXCR4 rs2322864 is associated with genetic risk of CAD, but not with the severity of coronary stenosis.
Project description:ImportancePhysiological stenosis assessment is recommended to guide percutaneous coronary intervention (PCI) in patients with stable angina.ObjectiveTo determine the association between all commonly used indices of physiological stenosis severity and angina-limited exercise time in patients with stable angina.Design, setting, and participantsThis cohort study included data (without follow-up) collected over 1 year from 2 cardiac hospitals. Selected patients with stable angina and physiologically severe single-vessel coronary artery disease presenting for clinically driven elective PCI were included.ExposuresFractional flow reserve (FFR), instantaneous wave-free ratio (iFR), hyperemic stenosis resistance (HSR), and coronary flow reserve (CFR) were measured invasively. Immediately after this, patients maximally exercised on a catheter-table-mounted supine ergometer until they developed rate-limiting angina. Subsequent PCI was performed in most patients, followed by repeat maximal supine exercise testing.Main outcomes and measuresAssociations between FFR, iFR, HSR, CFR, and angina-limited exercise time were assessed using linear regression and Pearson correlation coefficients. Additionally, the associations between the post-PCI increment in exercise time and baseline FFR, iFR, HSR, and CFR were assessed.ResultsTwenty-three patients (21 [91.3%] of whom were male; mean [SD] age, 60.6 [8.1] years) completed the pre-PCI component of the study protocol. Mean (SD) stenosis diameter was 74.6% (10.4%). Median (interquartile range [IQR]) values were 0.54 (0.44-0.72) for FFR, 0.53 (0.38-0.83) for iFR, 1.67 (0.84-3.16) for HSR, and 1.35 (1.11-1.63) for CFR. Mean (SD) angina-limited exercise time was 144 (77) seconds. Anatomical stenosis characteristics were not significantly associated with angina-limited exercise time. Conversely, FFR (R2 = 0.27; P = .01), iFR (R2 = 0.46; P < .001), HSR (R2 = 0.39; P < .01), and CFR (R2 = 0.16; P < .05) were all associated with angina-limited exercise time. Twenty-one patients (19 [90.5%] of whom were male; mean [SD] age, 60.1 [8.2] years) competed the full protocol of PCI, post-PCI physiological assessment, and post-PCI maximal exercise. After PCI, the median (IQR) FFR rose to 0.91 (0.85-0.96), median (IQR) iFR to 0.98 (0.94-0.99), and median (IQR) CFR to 2.73 (2.50-3.12), while the median (IQR) HSR fell to 0.16 (0.06-0.37) (P < .001 for all). The post-PCI increment in exercise time was most significantly associated with baseline iFR (R2 = 0.26; P = .02).Conclusions and relevanceIn a selected group of patients with severe, single-vessel stable angina, FFR, iFR, HSR, and CFR were all modestly correlated with angina-limited exercise time to varying degrees. Notwithstanding the limited sample size, no clear association was demonstrated between anatomical stenosis severity and angina-limited exercise time.
Project description:Background Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome-wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble-based supervised learning, the Evolutionary Action-Machine Learning framework ranked each gene's ability to classify case and control samples and identified 79 significant associations. These were connected to known risk loci; enriched in cardiovascular processes like lipid metabolism, blood clotting, and inflammation; and enriched for cardiovascular phenotypes in knockout mouse models. Among them, INPP5F and MST1R are examples of potentially novel coronary artery disease risk genes that modulate immune signaling in response to cardiac stress. Conclusions We concluded that machine learning on the functional impact of coding variants, based on a massive amount of evolutionary information, has the power to suggest novel coronary artery disease risk genes for mechanistic and therapeutic discoveries in cardiovascular biology, and should also apply in other complex polygenic diseases.