Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Relation of circulating lncRNA GAS5 and miR-21 with biochemical indexes, stenosis severity, and inflammatory cytokines in coronary heart disease patients.

BACKGROUND: Long noncoding RNA GAS5 (lnc-GAS5) and its target microRNA-21 (miR-21) regulate blood lipid, macrophages, Th cells, vascular smooth muscle cells to participate in atherosclerosis, and related coronary heart disease (CHD). The study aimed to further explore the linkage of their circulating expressions with common biochemical indexes, stenosis severity and inflammatory cytokines in CHD patients. METHODS: Ninety-eight CHD patients and 100 controls confirmed by coronary angiography were enrolled. Plasma samples were collected for lnc-GAS5 and miR-21 detection by reverse transcription-quantitative polymerase chain reaction and inflammatory cytokines determination by enzyme-linked immunosorbent assay. RESULTS: Lnc-GAS5 was increased in CHD patients compared with controls (2.270 (interquartile range [IQR]: 1.676-3.389) vs. 0.999 ([IQR: 0.602-1.409], p < 0.001), whereas miR-21 showed opposite tread (0.442 [IQR: 0.318-0.698] vs. 0.997 [IQR: 0.774-1.368], p < 0.001). In aspect of their intercorrelation, lnc-GAS5 negatively linked with miR-21 in CHD patients (p < 0.001) instead of controls (p = 0.211). Interestingly, among the common biochemical indexes, lnc-GAS5 related to decreased high-density lipoprotein cholesterol (p = 0.008) and increased C-reactive protein (CRP) (p < 0.001), while miR-21 correlated with lower total cholesterol (p = 0.024) and CRP (p < 0.001) in CHD patients. As stenosis degree, lnc-GAS5 positively correlated with Gensini score (p < 0.001), but miR-21 exhibited negative association (p = 0.003) in CHD patients. In terms of inflammatory cytokines, lnc-GAS5 positively related to tumor necrosis factor α (TNF-α) and interleukin (IL)-17A, while miR-21 negatively linked with TNF-α, IL-1ß, IL-6, and IL-17 in CHD patients (all p < 0.05). CONCLUSION: Circulating lnc-GAS5 and its target miR-21 exhibit potency to serve as biomarkers for CHD management.

Circulating ANGPTL3 and ANGPTL4 levels predict coronary artery atherosclerosis severity.

BACKGROUND: We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis. METHODS: A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits. RESULTS: According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively. CONCLUSIONS: Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.

Numerical modelling of blood rheology and platelet activation through a stenosed left coronary artery bifurcation.

Coronary bifurcations are prone to atherosclerotic plaque growth, experiencing regions of reduced wall shear stress (WSS) and increased platelet adhesion. This study compares effects across different rheological approaches on hemodynamics, combined with a shear stress exposure history model of platelets within a stenosed porcine bifurcation. Simulations used both single/multiphase blood models to determine which approach best predicts phenomena associated with atherosclerosis and atherothrombosis. A novel Lagrangian platelet tracking model was used to evaluate residence time and shear history of platelets indicating likely regions of thrombus formation. Results show a decrease in area of regions with pathologically low time-averaged WSS with the use of multiphase models, particularly in a stenotic bifurcation. Significant non-Newtonian effects were observed due to low-shear and varying hematocrit levels found on the outer walls of the bifurcation and distal to the stenosis. Platelet residence time increased 11% in the stenosed artery, with exposure times to low-shear sufficient for red blood cell aggregation (>1.5 s). increasing the risk of thrombosis. This shows stenotic artery hemodynamics are inherently non-Newtonian and multiphase, with variations in hematocrit (0.163-0.617) and elevated vorticity distal to stenosis (+15%) impairing the function of the endothelium via reduced time-averaged WSS regions, rheological properties and platelet activation/adhesion.

Increased expression of IL-20 is associated with ischemic cardiomyopathy and acute myocardial infarction.

Background: The expression and clinical significance of IL-20 in coronary artery diseases needs to be analyzed. Methods: IL-20 and its receptors were analyzed in coronary artery tissues. In a separate study, plasma IL-20 was also evaluated. Results: IL-20 and its receptors were significantly higher in coronary artery stenosis tissues from ischemic cardiomyopathy patients than that from controls. T lymphocytes and macrophages were the main source of IL-20 and expressed its receptors abundantly. Plasma IL-20 was significantly higher in acute myocardial infarction patients than that in controls. Conclusion: IL-20 was closely associated with the presence of acute myocardial infarction. IL-20 may participate in the progression of coronary artery stenosis and plaque vulnerability via regulating T lymphocytes and macrophages.

Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease.

BACKGROUND: The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD). METHODS: There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD. RESULTS: No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD. CONCLUSIONS: Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors.

Effects of Spironolactone on Hypoxia-Inducible Factor-1α in the Patients Receiving Coronary Artery Bypass Grafting.

ABSTRACT: We explored the protective effect of spironolactone on cardiac function in the patients undergoing coronary artery bypass grafting (CABG) by determining serum hypoxia-inducible factor-1α (HIF-1α) before and after CABG. We used the propensity score matching method retrospectively to select 174 patients undergoing CABG in our hospital from March 2018 to December 2019. Of the 174 patients, 87 patients taking spironolactone for more than 3 months before CABG were used as a test group and other 87 patients who were not taking spironolactone as a control group. In all patients, serum HIF-1α and troponin I levels were determined before as well as 24 hours and 7 days after CABG, serum N-terminal probrain natriuretic peptide (NT-proBNP) level was determined before as well as 12, 24, and 36 hours after CABG, and electrocardiographic monitoring was performed within 36 hours after CABG. The results indicated that there were no significant differences in the HIF-1α level between the test group and the control group before and 7 days after CABG, but the HIF-1α level was significantly lower in the test group than that in the control group 24 hours after CABG (P < 0.01). The 2 groups were not significantly different in the troponin I level at any time point. There was no significant difference in the serum NT-proBNP level between the test group and the control group before CABG, but NT-proBNP (BNP) levels were all significantly lower in the test group than those in the control group at postoperative 12, 24, and 36 hour time points (all P <0.05). The incidence of postoperative atrial fibrillation was also significantly lower in the test group than that in the control group (P = 0.035). Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease.

INTRODUCTION: The inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established. OBJECTIVES: The study investigates the levels of C reactive protein (CRP), interleukin 1ß (IL-1ß) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group. RESULTS: In the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1ß showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= -0.43, p=.05). IL-1ß weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= -0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= -0.41, p=.003). CONCLUSIONS: CRP, IL-1ß and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.

Serum levels of IL-32 in patients with coronary artery disease and its relationship with the serum levels of IL-6 and TNF-α.

The coronary artery disease (CAD) is a chronic inflammatory disease caused by atherosclerosis, in which arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a proinflammatory cytokine, which enhances inflammation through inducing the secretion of different inflammatory cytokines. The main objective of the current study was to assess the serum levels of IL-32 in subjects with obstructive CAD and its relationship with the serum levels of IL-6 and TNF-α. This study was performed on 42 subjects with obstructive CAD and 42 subjects with non-obstructive CAD. The serum levels of TNF-α, IL-6, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). The serum levels of TNF-α, IL-6, and IL-32 were 3.2, 3.48, and 2.7 times higher in obstructive CAD compared to non-obstructive CAD, respectively. Moreover, the serum levels of TNF-α and IL-32 in obstructive CAD with cardiac arterial stenosis in one major vessel were significantly higher than the levels in obstructive CAD with cardiac arterial stenosis in more than one major vessel. ROC curve analysis revealed that the serum levels of TNF-α, IL-6, and IL-32 were good predictors of obstructive CAD. Moreover, multiple logistic regression analyses suggested that the serum levels of TNF-α, IL-6, IL-32, LDL, and ox-LDL were independently related to the presence of obstructive CAD, while serum levels of HDL were not. TNF-α, IL-32, and IL-6 showed an increase in obstructive CAD, and the serum levels of these cytokines showed a satisfactory ability for predicting obstructive CAD.

HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome.

BACKGROUND: Emerging evidence demonstrates that the lipid metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) differs from nondiabetic patients. However, the distinct lipid profiles and their relationships with the severity of coronary artery stenosis and prognosis in patients with T2DM remain elusive. METHOD AND RESULT: This single-center, prospective cohort study enrolled 468 patients diagnosed with ACS undergoing coronary angiography, consisting of 314 non-DM and 154 DM patients. The HDL-C/apoA-I ratio was significantly higher in DM patients with a multivessel (≥3 affected vessels) lesion than a single-vessel (1-2 affected vessels) lesion. Regression analyses showed that the HDL-C/apoA-I ratio was positively correlated to the number of stenotic coronary arteries in DM patients but not non-DM patients. However, Kaplan-Meier survival analysis revealed no significant difference in the major adverse cardiovascular event rate regarding different HDL-C/apoA-I levels in DM or non-DM ACS patients at the end of the 2-year follow-up. CONCLUSION: A higher HDL-C/apoA-I ratio is associated with increased severity of coronary artery stenosis in DM patients with ACS but not with the rate of major adverse cardiovascular events at the end of the 2-year follow-up.

Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG). METHODS: This prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions. RESULTS: Serum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05). CONCLUSION: Serum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.

Image-derived mean velocity measurement for prediction of coronary flow reserve in a canonical stenosis phantom using magnetic particle imaging.

INTRODUCTION: Aim of this study is to evaluate whether magnetic particle imaging (MPI) is capable of measuring velocities occurring in the coronary arteries and to compute coronary flow reserve (CFR) in a canonical phantom as a preliminary study. METHODS: For basic velocity measurements, a circulation phantom was designed containing replaceable glass tubes with three varying inner diameters, matching coronary-vessel diameters. Standardised boluses of superparamagnetic-iron-oxide-nanoparticles were injected and visualised by MPI. Two image-based techniques were competitively applied to calibrate the respective glass tube and to compute the mean velocity: full-duration-at-half-maximum (FDHM) and tracer dilution (TD) method. For CFR-calculation, four necessary settings of the circulation model of a virtual vessel with an inner diameter of 4 mm were generated using differently sized glass tubes and a stenosis model. The respective velocities in stenotic glass tubes were computed without recalibration. RESULTS: On velocity level, comparison showed a good agreement (rFDHM = 0.869, rTD = 0.796) between techniques, preferably better for 4 mm and 6 mm inner diameter glass tubes. On CFR level MPI-derived CFR-prediction performed considerably inferior with a relative error of 20-44%. CONCLUSIONS: MPI has the ability to reliably measure coronary blood velocities at rest as well as under hyperaemia and therefore may be suitable for CFR calculation. Calibration-associated accuracy of CFR-measurements has to be improved substantially in further studies.

rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography.

BACKGROUND AND AIMS: Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients. METHODS AND RESULTS: The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG. The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04-1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04-1.96) and 1.39 (1.22-1.58) respectively]. CONCLUSIONS: rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.

Relationship between neutrophils to HDL-C ratio and severity of coronary stenosis.

BACKGROUND: Lipid and inflammatory molecules play a key role in the development of inflammation. Neutrophil counts are used as markers of inflammation duration, and HDL-C is used as an anti-atherosclerosis component. However, few studies have been found to integrate these two indicators to explore coronary stenosis. We suggested that neutrophil count as a marker of inflammation persistence and HDL-C as an anti-atherosclerotic component should be integrated into a single biomarker NHR to explore its correlation with CAD degree and predict the severity of coronary stenosis among CAD patients. METHODS: We examined 404 eligible patients who underwent coronary angiography. Based on the results of coronary angiography, patients in CAD+ group (n = 155) were defined as those having angiographic coronary stenosis of at least 50% lumen reduction in at least one major coronary artery (including left anterior descending artery, left circumflex artery, left main coronary artery, right coronary artery). Patients with luminal stenosis but no more than 50% were defined as CAD- group (n = 49), and patients without luminal stenosis (n = 200) were regarded as control group. The relationship between various serum markers and the severity of coronary stenosis was examined by Spearman correlation analysis. Logistic regression analysis was performed to identify the influencing factors of the severity of coronary artery disease. RESULTS: The modified Gensini score was positively correlated with neutrophil HDL-C ratio and negatively correlated with albumin and HDL-C. Multiple regression analysis showed that neutrophil HDL-C ratio were significantly associated with CAD. Neutrophil HDL-C ratio is an independent predictor of CAD. The ROC analysis provided a cut-off value of 1.51 for neutrophil HDL-C ratio to predict CAD with 94.8% sensitivity and 0.024 Yoden index, and area under the ROC curve of 0.617 (95% CI 0.560-0.675, P < 0.001). CONCLUSION: Neutrophil HDL-C ratio is not only closely related to coronary artery stenosis, but also an independent predictor of severe coronary stenosis.

Predictive value of miRNA-21 on coronary restenosis after percutaneous coronary intervention in patients with coronary heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Evidence reveals that microRNA (miRNA) can predict coronary restenosis in patients suffering from coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Perhaps, miRNA-21 is a promising biomarker for the diagnosis of coronary restenosis after PCI. However, the accuracy of miRNA-21 has not been systematically evaluated. Therefore, it is necessary to perform meta-analysis to certify the diagnostic values of miRNA-21 on coronary restenosis after PCI. METHODS: China National Knowledge Infrastructure, Wanfang, VIP, and China Biology Medicine disc, PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant studies to explore the potential diagnostic values of miRNA-21 on coronary restenosis after PCI from inception to January 2021. All data were extracted by 2 experienced researchers independently. The risk of bias about the meta-analysis was confirmed by the Quality Assessment of Diagnostic Accuracy Studies-2. The data extracted were synthesized and heterogeneity was investigated as well. All of the above statistical analyses were carried out with Stata 16.0. RESULTS: This study proved the pooled diagnostic performance of miRNA-21 on coronary restenosis after PCI. CONCLUSION: This study clarified confusions about the specificity and sensitivity of miRNA-21 on coronary restenosis after PCI, thus further guiding their promotion and application. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/356QK.

Association of dipeptidyl peptidase IV polymorphism, serum lipid profile, and coronary artery stenosis in patients with coronary artery disease and type 2 diabetes.

ABSTRACT: Cardiovascular disease (CAD) is a devastating illness, but to date there are limited means of predicting a person's coronary stenosis severity and their prognosis. The study was performed to investigate the relationship between dipeptidyl peptidase 4(DPP4) gene polymorphisms and serum lipid profiles, as well as the severity of coronary artery stenosis in patients with CAD and type 2 diabetes (T2DM) for the first time.Herein, 201 patients with CAD and T2DM were enrolled in the Department of Cardiology, Shandong Provincial Qianfoshan Hospital. DPP4 rs3788979 and rs7608798 single nucleotide polymorphisms (SNPs) were genotyped. The general information of all patients was collected, and the associations between DPP4 SNPs and lipid profiles were detected. At the same time, association between SNP polymorphisms and the degree of coronary artery stenosis were analyzed.There was a significant difference in apolipoprotein B (ApoB) levels (P = .011) for the rs3788979 polymorphism, while no difference was identified in other blood lipids or with other mutations. SNP mutation of A to G in rs3788979 was associated with a reduced percentage of severe coronary artery stenosis in female patients (P = .023) as well as those with nosmoking (P = .030), nodrinking (P = 0.007), and nocardiovascular family history (P = 0.015).G allele of rs3788979 is associated with a reduced ApoB level. Besides, we suggest that G allele in rs3788979 may have a cardioprotective effect and prove to be a useful and specific measure when predicting a patient's coronary stenosis severity if diagnosed with CAD and T2DM.

Circulating PGLYRP1 Levels as a Potential Biomarker for Coronary Artery Disease and Heart Failure.

ABSTRACT: Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE-/- mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.

Effect of ABCA1 promoter methylation on premature coronary artery disease and its relationship with inflammation.

BACKGROUND: ATP-binding cassette transporter A1 (ABCA1) plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects. Increased ABCA1 promoter methylation level may result in the progression of coronary artery disease. Thus, the present study investigated the association between promoter methylation status of ABCA1 and inflammation in the development of premature coronary artery disease (pCAD). METHODS: PCAD patients and healthy individuals (n = 90 each) were recruited from the Characteristic Medical Center of the Chinese People's Armed Police Force from June to December 2019. Using pyrosequencing, the levels of ABCA1 promoter methylation in their blood samples were evaluated. Serum concentrations of lipids, interleukin 1ß (IL-1ß), C-reactive protein (CRP), and circulating free DNA/Neutrophil extracellular traps (cfDNA/NETs) were also routinely measured and compared between the two groups. P values < 0.05 were considered statistically significant. RESULTS: The mean ABCA1 promoter methylation levels were significantly higher in the pCAD group than in the control group (44.24% ± 3.66 vs. 36.05% ± 2.99, P < 0.001). Based on binary logistic regression analysis, ABCA1 promoter methylation level was identified as an independent risk factor for pCAD development (odds ratio = 2.878, 95% confidence interval: 1.802-4.594, P < 0.001). Furthermore, ABCA1 promoter methylation levels were negatively correlated with HDL levels (r = - 0.488, P < 0.001) and positively correlated with the levels of CRP, cfDNA/NETs, and IL-1ß (r = 0.389, 0.404, 0.385, respectively; P < 0.001). Multiple regression analysis showed that the serum levels of CRP, IL-1ß, and cfDNA/NETs independently affect ABCA1 promoter methylation. CONCLUSIONS: Our findings indicate that high methylation levels at the ABCA1 promoter are associated with low HDL cholesterol levels and an increased risk of pCAD. Inflammatory factors and NETs may be involved in the progression of pCAD by affecting ABCA1 promoter methylation levels.

The correlation between lipoprotein(a) and coronary atherosclerotic lesion is stronger than LDL-C, when LDL-C is less than 104 mg/dL.

BACKGROUND: Lp(a) and LDL-C are both risk factors of atherosclerotic cardiovascular disease (ASCVD). But there was a contradiction point in LDL-C and Lp(a) control. The appropriate level of LDL-C and Lp(a) in the prevention of ASCVD is still pending. OBJECTIVE: To investigate the correlation of Lp(a) and coronary atherosclerotic lesion, and find out the balance point in LDL-C and Lp(a) control. METHOD: 3449 patients were divided to coronary atherosclerotic heart disease (CAHD) Group and Non-CAHD Group based on the result of coronary angiography. The clinical characteristics were compared, and Logistic regressions were applied to find the CAHD risk factors in total, High-LDL-C Group (LDL-C ≥ 100 mg/dL) and Low-LDL-C Group (LDL-C < 100 mg/dL) patients. Spearman correlation analysis of Lp(a), LDL-C and Gensini Score was performed in patients with different LDL-C concentration. RESULTS: Except male and diabetes, the traditional CAHD risk factors were well matched between two groups. But triglyceride, LDL-C and Lp(a) were higher, HDL-C and Apo-A1 were lower in CAHD group (2771). In the Logistic regression analysis, diabetes, LDL-C and Lp(a) are risk factors of CAHD in all patients, while in High-LDL-C Group, they were age, LDL-C, non-HDL-C and ApoB, in Low-LDL-C Group, they were age, Lp(a) and ApoB. Lp(a) correlated with Gensini with coefficient r = 0.41 in all patients, 0.67 in Low-LDL-C Group and 0.32 in High-LDL-C Group. The coefficient r for Lp(a) and Gensini decreased, while the r for LDL-C and Gensini increased with LDL-C concentration increasing. The two fitted lines of rs crossed at LDL-C = 2.7 mmol/L (104 mg/dL). CONCLUSION: Lp(a) was the risk factor of CAHD in patients with LDL-C < 100 mg/dL. The correlation between Lp(a) and Gensini was influenced by LDL-C concentration, and the correlation was stronger than LDL-C when LDL-C < 104 mg/dl.

FGF-23 correlates with endocrine and metabolism dysregulation, worse cardiac and renal function, inflammation level, stenosis degree, and independently predicts in-stent restenosis risk in coronary heart disease patients underwent drug-eluting-stent PCI.

BACKGROUND: The present study aimed to assess the correlation of fibroblast growth factor (FGF)-23 expression with clinical characteristics, then further explore its value in predicting 2-year in-stent restenosis (ISR) risk in coronary heart disease (CHD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES). METHODS: In this prospective, single-center, observational study, totally 214 CHD patients treated by PCI with DES were consecutively recruited, and peripheral blood samples were collected prior to PCI with DES for serum samples isolation. Following, FGF-23 level in the serum samples was detected via enzyme linked-immuno-sorbent Assay. The follow-up coronary angiography was performed at 1 year and 2 years after PCI or if suspected ISR symptoms occurred. RESULTS: FGF-23 was positively correlated with fasting blood-glucose, insulin resistance, serum creatinine, serum uric acid, LDL-C, high-sensitivity C-reactive protein, cardiac troponin I and N-terminal-proB-type natriuretic peptide, while was negatively associated with HDL-C and left ventricular ejection fraction (all P < 0.01). Furthermore, FGF-23 was positively correlated with hypercholesteremia, hyperuricemia and family history of CAD (all P < 0.05). However, it did not correlate with other chronic complications, biochemical indexes, lesion features or PCI parameters (all P > 0.05). Moreover, FGF-23 level was higher in 2-year ISR patients (n = 38) compared to 2-year non-ISR patients (n = 176) (P < 0.001), and receiver operating characteristic curve indicated that FGF-23 was of good value in predicting 2-year ISR risk (AUC 0.828, 95% CI 0.761-0.896). CONCLUSION: FGF-23 correlates with endocrine and metabolism dysregulation, worse cardiac and renal function, inflammation level, stenosis degree of target lesion, and serves as an independent risk factor for 2-year ISR risk in CHD patients underwent PCI with DES.