Pathogenesis Of Coronary Heart Disease Research Articles

The Pathogenesis of Coronary Heart Disease and the Treatment Ideas and Medication of Traditional Chinese and Western Medicine

The Pathogenesis of Coronary Heart Disease and the Treatment Ideas and Medication of Traditional Chinese and Western Medicine

Predictive value of system immune-inflammation index for the severity of coronary stenosis in patients with coronary heart disease and diabetes mellitus

Coronary heart disease (CHD) has been recognized as a chronic progressive inflammatory disorder, and Diabetes mellitus (DM) is an independent risk factor for the pathogenesis of CHD. Recent research has underscored the systemic immune-inflammation index (SII) as a potent prognostic indicator for individuals suffering from acute coronary syndrome (ACS). This study aimed to delve into the relationship between SII and the degree of coronary atherosclerotic stenosis in non-acute myocardial infarction patients with or without DM. We enrolled a total of 2760 patients with cardiovascular disease between November 2023 and May 2024. All eligible participants were divided into the CHD group and the DM & CHD group according to the existence of comorbid DM. Our study revealed that the SII values were significantly higher in diabetic patients with CHD compared to those with CHD alone (P < 0.05). Furthermore, among patients with both CHD and DM, higher SII values were associated with a greater likelihood of developing complex, triple-branch coronary artery lesions, while the opposite trend was observed in CHD populations (P < 0.05). In the regression model completely adjusted for potential confounders, the correlation between high SII levels and co-existing DM status in CHD patients persisted as statistically significant even after attaining guideline-recommended LDL-C and TG goals (P < 0.05). Moreover, our findings demonstrated a significant link between SII levels and the severity of coronary artery stenosis as assessed by coronary angiography, particularly in the DM and CHD patient cohorts (P < 0.05). Further stratified analysis revealed a novel finding that SII levels in DM and CHD patients maintained a positive linear relationship with coronary plaque burden even under stringent glycemic control (P < 0.01, r = 0.37), whereas this correlation was absent in CHD patients who had FBG of 7 mmol/L or lower upon admission (P < 0.01, r < 0.30). These important findings underscore the SII as an independent predictor of the severity of coronary plaque burden in diabetic patients with CHD, offering valuable insights that can aid clinicians in refining risk stratification and implementing personalized management strategies for those at elevated risk.

Exploring causal correlations between inflammatory cytokines and coronary heart disease: A Mendelian randomization study.

Coronary heart disease (CHD) is a global health concern, with inflammation significantly contributing to its pathogenesis. It is crucial to understand the relationship between inflammatory cytokines and CHD. This study investigates the causal correlations between circulating inflammatory cytokines and CHD using Mendelian randomization (MR), assessing both causative and resultant roles of these cytokines in CHD. In this bidirectional MR analysis, we used genetic data from a genome-wide association study (GWAS) of 60,801 CHD cases and 123,504 controls of European ancestry. We derived inflammatory cytokine data from a GWAS summary of 14,824 participants. The primary analytical approach was the inverse variance-weighted (IVW) method, supported by MR-Egger, weighted median, and weighted mode analyses. Heterogeneity was assessed using the Cochrane Q test, and horizontal pleiotropy was evaluated through the MR-Egger intercept and the MR-PRESSO global test, ensuring robustness against potential pleiotropic bias. This study pinpointed several cytokines as key upstream influencers on the risk of CHD, including eotaxin (CCL11) (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.03-1.18, P = .003), C-C motif chemokine ligand 20 (CCL20) (OR: 1.15, 95% CI: 1.05-1.25, P = .002), macrophage colony-stimulating factor 1 (CSF1) (OR: 1.09, 95% CI: 1.01-1.17, P = .020), Fibroblast growth factor 21 (FGF21) (OR: 1.14, 95% CI: 1.01-1.29, P = .038), Fms-related tyrosine kinase 3 ligand (FLT3LG) (OR: 1.26, 95% CI: 1.09-1.44, P = .001), neurotrophin-3 (NT-3) (OR: 1.12, 95% CI: 1.01-1.24, P = .026), and leukemia inhibitory factor (LIF) (OR: 0.89, 95% CI: 0.80-0.99, P = .029). Conversely, T-cell surface glycoprotein CD5 (CD5) (beta: -0.15, 95% CI: -0.29 to -0.01, P = .042) were identified as downstream factors impacted by CHD. No evidence of heterogeneity or horizontal pleiotropy was detected across all results, and a leave-one-out analysis substantiated the robustness of these findings. These findings suggest that CCL11, CCL20, CSF1, FGF21, FLT3LG, NT-3, and LIF may play a crucial role in the pathogenesis of CHD. Additionally, CHD may impact the expression of CD5. Additional research is needed to explore the potential of these biomarkers in the prevention and treatment of CHD.

Coronary heart disease: innovative understanding from traditional Chinese medicine and treatment by classic formulas

Coronary heart disease is a common cardiovascular disease, attacking about 11.4 million patients in China. With increasing prevalence and mortality year by year, coronary heart disease has become a major factor threatening human health and public health. Although primary and secondary prevention, intervention, coronary artery bypass grafting and other interventions have reduced the death rate, there are drug(aspirin) resistance, secondary nitroglycerin failure, post-intervention fatigue, chest tightness, and an-xiety, and complication with a high risk of bleeding, which have become the key clinical and scientific issues needed to be resolved. Coronary heart disease belongs to the category of chest impediment and heart pain in traditional Chinese medicine(TCM). The TCM etiology of this disease includes external contraction of cold, emotional disorders, constitutional insufficiency, physical weakness, and labor injury, which are closely related to sympathetic nerve activity, state of cardiac and psychological diseases, family history, and cardiovascular metabolic disorders in modern medicine. The TCM causes of coronary heart disease include Qi depression, phlegm turbidity, blood stasis, fire-heat, cold congealing, and healthy Qi deficiency, which are associated with emotional factors such as anxiety and depression, abnormal lipid metabolism, abnormalities in blood circulation and coagulation, inflammatory responses, hyperactive immune responses, and heart failure, chronic wasting disease, or aging, respectively. Accordingly, the patients with Qi depression should be treated with Chaihu Longgu Muli Decoction, and those with phlegm turbidity should be treated with Wendan Decoction and Gualou Xiebai Banxia Decoction. Xuefu Zhuyu Decoction and Guizhi Fuling Pills are recommended for blood stasis, Xiaoxianxiong Decoction and Sanhuang Xiexin Decoction for fire-heat, Zhishi Xiebai Guizhi Decoction for cold congealing, and Renshen Decoction for healthy Qi deficiency. Due to the changes in the spectrum of diseases from ancient to modern times as well as the differences in physical constitution, the key cause of coronary heart disease has evolved from the chest Yang deficiency and cold congealing to Qi depression, phlegm turbidity, phlegm combined with stasis, and fire-heat, showing a shift from cold to heat and from deficiency to excess. The combination of classic formulas presents a pattern. That is, the core formula-syndrome correspondence of a disease often fixedly appears with other formula-syndrome correspondence, which may be related to the development of the pathophysiological mechanism of the disease. In the clinical application of modern pharmacological results, the research team has formulated the clinical principle of pathogenesis corresponding to pathological changes and medicinal nature corresponding pharmacological effects. The modern pharmacological research on classic formulas is conducive to targeted treatment. Moreover, classic formulas help to ameliorate aspirin resistance, clopidogrel resistance, post-intervention anxiety, and high risk of bleeding and address the lack of effective blockade of critical lesions in the coronary artery and the progression of post-infarction heart failure. The innovative understanding of the etiology and pathogenesis of co-ronary heart disease helps to improve the clinical efficacy of TCM and the clinical system for treating coronary heart disease with classic formulas.

The effect of antiphospholipid antibodies on the frequency of extrasystoles in men with coronary heart disease and and myocardial infarction

Abstract Background Coronary heart disease (CHD) is one of the most socially significant diseases of the cardiovascular system. Acute myocardial infarction (MI) develops 10 years earlier in men than in women. Manifestation of MI in young men quite often happen without clinically significant stenosis of coronary vessels. And fatal arrhythmias are one of the main causes of death in patient with cardiovascular diseases. Purpose To evaluate the clinical and pathogenetic significance of antiphospholipid antibodies (aPL) in patients with MI and disorders of rythm. Methods 107 patients men (average age 51.2 ± 6.15 years) with CHD and MI were examined. The content of aPL IgG - antibodies to cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylacetate in the blood serum were determined by enzyme-linked immunosorbent assay and electrocardiography Holter monitor 24 hours tests were done. Results aPL IgG were detected in 56 patients (52,3% of the total number of patients with MI), it concentration threshold 10 GPL U/ml in blood serum. The median age of first acute MI in men 56 years, according to the literary data. In our investigation average age of aPL positive patients is 44.8 ± 5.47 years. They had first MI on average 12 years earlier than general population. The level of aPL IgG in blood serum was higher in 1,7 times (19,3 ± 7,32 GPL U/ml and 11,4 ± 5,41 GPL U/ml (p &amp;lt;0.05) in patients with recurrent MI compared to one MI. Also the results of the study showed that the highest prevalence of polytopic extrasystoles is observed among aPL positive CHD patients with recurrent MI (68,3%) compared to one MI in anamnesis (26,3%). Moreover, 23.2% of people who had recurrent MI had ventricular extrasystole of high gradations. It is important to note, that іn patients with first Q-MI levels of aFL IgG were in 1.27 times higher (p&amp;lt;0.05) than in patients with first non-Q-MI. And the frequency of the polytopic extrasystoles was on 38% higher (p&amp;lt;0.01) іn patients with first Q-MI compared to patients with first non-Q-MI. Conclusion The results obtained by us indicate the possible involvement of the autoimmune factor, in particular aPL IgG, in the pathogenesis of CHD. Positive correlation of aPL IgG with the frequency of rhythm disorders indicates the severity of condition in men with CHD and MI in anamnesis and need for further research.

Circulating metabolites and coronary heart disease: a bidirectional Mendelian randomization.

Numerous studies have established a link between coronary heart disease and metabolic disorders. Yet, causal evidence connecting metabolites and Coronary Heart Disease (CHD) remains scarce. To address this, we performed a bidirectional Mendelian Randomization (MR) analysis investigating the causal relationship between blood metabolites and CHD. Data were extracted from published genome-wide association studies (GWASs) on metabolite levels, focusing on 1,400 metabolite summary data as exposure measures. Primary analyses utilized the GWAS catalog database GCST90199698 (60,801 cases and 123,504 controls) and the FinnGen cohort (43,518 cases and 333,759 controls). The primary method used for causality analysis was random inverse variance weighting (IVW). Supplementary analyses included MR-Egger, weighted mode, and weighted median methods. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Reverse MR analysis was employed to evaluate the direct impact of metabolites on coronary heart disease. Additionally, replication and meta-analysis were performed. We further conducted the Steiger test and colocalization analysis to reflect the causality deeply. This study identified eight metabolites associated with lipids, amino acids and metabolite ratios that may influence CHD risk. Findings include: 1-oleoyl-2-arachidonoyl-GPE (18:1/20:4) levels: OR = 1.08; 95% CI 1.04-1.12; P = 8.21E-06; 1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) levels: OR = 1.07; 95% CI 1.04-1.11; P = 9.01E-05; Linoleoyl-arachidonoyl-glycerol (18:2/20:4): OR = 1.08; 95% CI 1.04-1.22; P = 0.0001; Glycocholenate sulfate: OR = 0.93; 95% CI 0.90-0.97; P = 0.0002; 1-stearoyl-2-arachidonoyl-GPE (OR = 1.07; 95% CI 1.03-1.11; P = 0.0002); N-acetylasparagine (OR = 1.04; 95% CI 1.02-1.07; P = 0.0030); Octadecenedioate (C18:1-DC) (OR = 0.93; 95% CI 0.90-0.97; P = 0.0004); Phosphate to linoleoyl-arachidonoyl-glycerol (18:2-20:4) (1) ratio (OR = 0.92; 95% CI 0.88-0.97; P = 0.0005). The integration of genomics and metabolomics offers novel insights into the pathogenesis of CHD and holds significant importance for the screening and prevention of CHD.

Role of inflammatory signaling pathways involving the CD40–CD40L–TRAF cascade in diabetes and hypertension—insights from animal and human studies

CD40L–CD40–TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L–CD40–TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipidemia plus diabetes (db/db mice) or hypertension (1 mg/kg/d angiotensin-II for 7 days), TRAF6 inhibitor treatment (2.5 mg/kg/d for 7 or 14 days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L–CD40–TRAF signaling cascade and their associated inflammatory pathways are expressed in CHD patients suffering from comorbidities. Therefore, we analyzed vascular bypass material (aorta or internal mammary artery) and plasma from patients with CHD with diabetes and/or hypertension. Our Olink targeted plasma proteomic analysis using the IMMUNO-ONCOLOGY panel revealed a pattern of step-wise increase for 13/92 markers of low-grade inflammation with significant changes. CD40L or CD40 significantly correlated with 38 or 56 other inflammatory targets. In addition, specific gene clusters that correlate with the comorbidities were identified in isolated aortic mRNA of CHD patients through RNA-sequencing. These signaling clusters comprised CD40L–CD40–TRAF, immune system, hemostasis, muscle contraction, metabolism of lipids, developmental biology, and apoptosis. Finally, immunological analysis revealed key markers correlated with comorbidities in CHD patients, such as CD40L, NOX2, CD68, and 3-nitrotyrosine. These data indicate that comorbidities increase inflammatory pathways in CHD, and targeting these pathways will be beneficial in reducing cardiovascular events in CHD patients with comorbidities.

Identification of Plasma Exosomes hsa_circ_0001360 and hsa_circ_0000038 as Key Biomarkers of Coronary Heart Disease.

Coronary heart disease (CHD) is the leading cause of death and disability worldwide. Accumulating evidence reveals that atherosclerosis (AS), characterized by systemic, chronic, and multifocal disease, and is the primary pathological basis of cardiovascular diseases, including CHD. However, the molecular underpinnings of CHD are still far from well understood. Our study attempted to identify aberrant plasma exosome-derived circRNAs and key exosomal circRNA biomarkers for CHD. The expression profiles of mRNAs, circRNAs, and lncRNAs in the blood exosomes of CHD patients and healthy controls were obtained from the exoRBase database. The corresponding miRNAs of the differentially expressed mRNAs, circRNAs, and lncRNAs were predicted via ENCORI and the miRcode database. LncRNAs/circRNAs and mRNAs with the cotargeted miRNAs were selected to construct an interaction network. Multiple machine learning algorithms have been used to explore potential biomarkers, followed by verification in patients with CHD using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Based on the cutoff criterion of P < 0.05, we identified 85 differentially expressed circRNAs (4 upregulated and 81 downregulated), 43 differentially expressed lncRNAs (24 upregulated and 19 downregulated), and 312 differentially expressed mRNAs (55 upregulated and 257 downregulated). Functional enrichment analysis revealed that the differentially expressed mRNAs were involved mainly in neutrophil extracellular trap (NET) formation and the nucleotide-binding oligomerization domain- (NOD-) like receptor signaling pathway. Further analysis revealed that the DEGs in the circRNA/lncRNA-miRNA-mRNA interaction network were closely related to lipid and atherosclerotic signaling pathways. Hsa_circ_0001360 and hsa_circ_0000038 were identified as potential biomarkers for CHD based on three machine learning algorithms. The relative expression levels of hsa_circ_0001360 and hsa_circ_0000038 were significantly altered in plasma exosomes from patients with CHD. ROC curve analysis revealed that the areas under the curve (AUCs) were 0.860, 0.870, and 0.940 for hsa_circ_0001360, hsa_circ_0000038, and the two-gene combination, respectively. The circRNA/lncRNA-miRNA-mRNA interaction network might help to elucidate the pathogenesis of CHD. Hsa_circ_0001360 combined with hsa_circ_0000038 might be an important diagnostic biomarker.

Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease

ABSTRACT Objective The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). Methods We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What’s more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. Results Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. Conclusion Our results suggest that NINJ2 polymorphisms are associated with CHD risk.

Role of low-density lipoprotein in mediating the effect of air pollution on coronary heart disease: a two-step multivariate Mendelian randomization study.

Air pollution is affecting the health of millions of people all over the world. The causal correlations of PM2.5, PM10, and nitrogen dioxide (NOx), as the main fine particulate matter, and coronary heart disease (CHD) are yet to be explored. Low-density lipoprotein (LDL) has been a principal factor in the pathogenesis of CHD. It is an interesting issue to consider whether LDL mediates the effect of air pollutants in CHD pathogenesis. A genome-wide association study (GWAS) on the European population, followed up from 2010 to 2018, involving over 400,000 participants, was based on a land-use regression model. The annual mean concentrations of major air pollutant particles, PM2.5 (n=423,796), PM10 (n=423,796), and NOx (n=456,380), were recorded. The large GWAS database of CHD covered over ten million SNPs with independent single nucleotide polymorphisms (SNPs). LDL database collected major biochemical blood parameters from over 400,000 patients (n=440,546). Taken together, we conducted independent two-sample Mendelian randomization (MR) analyses for the causality between air pollutants (PM2.5, PM10, and NOx) and CHD. Multivariate MR analysis was conducted using causal relationships to determine the direct effects of exposure on outcome. The fixed-effect inverse variance weighted (IVW2) method was mainly employed to assess this relationship, with a confidence interval of 95% for the odds ratio (OR). Also, MR-Egger, weighted median, maximum likelihood ratio method, and random-effects inverse variance-weighted (IVW1) method were adopted as supplementary methods. Two-sample MR results based on the IVW2 method suggested positive correlations between PM2.5 and CHD [OR 1.875 (1.279-2.748), p=0.001], PM10 and CHD [OR 2.586 (1.479-4.523), p=0.001], and NOx and CHD [OR 2.991 (2.021-4.427), p=4.37E-08]. The direct effect and mediating proportion were calculated using multivariable Mendelian randomization (MVMR). Lastly, the mediating proportions of LDL in the regulatory roles of PM2.5, PM10, and NOx in CHD were 2.82%, 4.73%, and 9.54%, respectively. PM2.5, PM10, and NOx share direct causal associations with CHD, and LDL performs a mediating role in this pathogenic process. Early prevention against air pollution (such as increasing green areas and reducing large-scale industrial dust emissions) and early lipid-lowering treatment can effectively prevent the occurrence of CHD.

Identification of iron metabolism-related genes in coronary heart disease and construction of a diagnostic model.

Coronary heart disease is a common cardiovascular disease, yferroptosiset its relationship with iron metabolism remains unclear. Gene expression data from peripheral blood samples of patients with coronary heart disease and a healthy control group were utilized for a comprehensive analysis that included differential expression analysis, weighted gene co-expression network analysis, gene enrichment analysis, and the development of a logistic regression model to investigate the associations and differences between the groups. Additionally, the CIBERSORT algorithm was employed to examine the composition of immune cell types within the samples. Eight central genes were identified as being both differentially expressed and related to iron metabolism. These central genes are mainly involved in the cellular stress response. A logistic regression model based on the central genes achieved an AUC of 0.64-0.65 in the diagnosis of coronary heart disease. A higher proportion of M0 macrophages was found in patients with coronary heart disease, while a higher proportion of CD8T cells was observed in the normal control group. The study identified important genes related to iron metabolism in the pathogenesis of coronary heart disease and constructed a robust diagnostic model. The results suggest that iron metabolism and immune cells may play a significant role in the development of coronary heart disease, providing a basis for further research.

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

MODERN VIEWS ON THE PATHOGENESIS OF IMMUNE DYSFUNCTION AGAINST THE BACKGROUND OF THE METABOLIC SYNDROME IN ISCHEMIC HEART DISEASE

Introduction. Today, the pathology of the cardiovascular system is one of the most common and fatal diseases. Cardiovascular diseases are the cause of disability among the younger and younger population. Taking into account the frequency of cardiovascular diseases, the severity of the course and their lethality, the study of this topic remains one of the most urgent problems of medicine, in particular cardiology.&#x0D; The aim of the study. Consider modern views on the pathogenesis of coronary heart disease against the background of metabolic syndrome and the role of the immune system.&#x0D; Conclusions. Ischemic heart disease is the leading cause of mortality in Ukraine and the world. In recent years, there has been convincing evidence of a significant prevalence of cardiovascular disease in patients with metabolic syndrome. The presence of concomitant metabolic syndrome in patients with coronary heart disease worsens the course of the underlying disease and has an unfavorable prognosis, and even fatal cases.&#x0D; Therefore, the detection of an increase in the level of body mass index, dyslipidemia, hyperglycemia, arterial hypertension in a patient strengthens the effects of each other, that is, they have a synergistic effect, and in general, the risk of developing CHD becomes quite high.&#x0D; IL-6 is one of the cytokines released by both macrophages and adipocytes and its levels have been shown to be increased in insulin resistance and obesity. In fact, IL-6 is known to regulate fat and glucose metabolism, mediating insulin resistance through various complex mechanisms. This cytokine acts on various tissues, leading to the metabolic effects of obesity. In the liver, IL-6 increases the production of acute phase reactants, including CRP. Several studies have demonstrated that high CRP levels have the strongest correlation with cardiac events, T2DM, and MS. IL-6 also contributes to a prothrombotic state by increasing the level of fibrinogen, another acute phase reactant. In addition, IL-6 targets other tissues, such as endothelial cells, to promote the expression of vascular cell adhesion molecules, leading to vascular wall atherosclerosis, inflammation, and dysfunction.&#x0D; These data support the role of IL-6 in the development of insulin resistance, but do not support the hypothesis that IL-6 is involved in β-cell failure.&#x0D; IL-18 is a pro-inflammatory cytokine associated with insulin resistance and T2DM risk. IL-18 stimulates the production of gamma interferon (IFN-γ), which, in turn, is probably involved in the pathogenesis of atherosclerosis. IL-18 is a cytokine that is a predictor of metabolic syndrome.&#x0D; TNFα is another cytokine produced in adipose tissue, mainly from local macrophages, and its production also varies with adipose tissue mass and correlates with insulin resistance, both hallmarks of MS. TNFα exerts its pathogenic effects by disrupting insulin signaling in adipocytes and hepatocytes through serine phosphorylation and inactivation of insulin receptors and downstream signaling molecules, leading to decreased metabolic effects of insulin. TNFα also contributes to insulin resistance by inducing hepatic lipolysis.

The mediation effect of HDL-C: Non-HDL-C on the association between inflammatory score and recurrent coronary events

BackgroundInflammation and lipids are both involved in the pathogenesis of coronary heart disease (CHD). However, the mediation effect of lipoproteins on the association between inflammation and recurrent coronary events in CHD patients remains unclear. MethodsThis was a retrospective study including CHD patients hospitalized in the Department of Cardiovascular Medicine in Sun Yat-sen Memorial Hospital between January 2011 and December 2012 with the endpoint of recurrent coronary events. The study calculated inflammatory score based on six serum inflammatory markers, including complement C3, complement C4, hyper-sensitive CRP, fibrinogen, D-dimer, and white blood cell count. Logistic regression analysis, subgroup analysis and mediation analysis were performed to assess the associations between inflammatory score and recurrent coronary events in different subpopulations and the identification of mediators. Inflammatory cytokine expression, cholesterol efflux capacity, and hepatic cholesterol influx were performed in additional CHD patients and healthy controls. ResultsThere were 191 CHD patients included in the analysis with a median inflammatory score of −0.78 (−2.17, 1.35) and 63 cases of recurrent coronary events. Subgroup logistic regression analysis demonstrated that inflammatory score was positively associated with recurrent coronary events only in the diabetic subgroup [OR: 1.241 (1.004, 1.534), P < 0.046]. HDL-cholesterol (HDL-C): non-HDL-C performed 46.74 % of negative mediation effect on this association. CHD patients had lower cholesterol efflux capacity than healthy controls, which was mediated by HDL: non-HDL ratio of 0.4. No difference was found in hepatic cholesterol influx between the two groups. ConclusionInflammatory score was associated with recurrent coronary events mediated by HDL-C: non-HDL-C ratio in diabetic CHD patients, indicating that lipoproteins might aggravate the inflammatory effect on atherosclerosis under hyperglycemia. Our findings suggested that anti-inflammatory and lipid-lowering therapies might be beneficial for this population.

CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case–control study

PurposeThe research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk.MethodsThis case–control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection.ResultsAs a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09–1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06–1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN).ConclusionThis study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Characterization of lncRNA-associated ceRNA network to uncover novel potential biomarkers in coronary artery disease.

The purpose of this study was to construct a competitive endogenous RNA (ceRNA) network related to long non-coding RNA (lncRNAs) via the bioinformatics analysis, reveal the pathogenesis of coronary heart disease (CAD) and develop new biomarkers for CAD. The gene expression datasets of peripheral blood of CAD were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were identified. Subsequently, a ceRNA network involving lncRNAs, miRNAs, and mRNAs was built. Moreover, DElncRNAs in the cytoplasm were screened and a DElncRNA-associated ceRNA network was established. In total, 1860 DEmRNAs, 393 DElncRNAs and 20 DEmiRNAs were filtrated in patients with CAD compared with normal controls. Functional analysis suggested that DEmRNAs significantly enriched in CAD-related pathways, such as PI3K-Akt signaling pathways and MAPK signaling pathway. The ceRNA network contained 12 DEmiRNAs, 30 DElncRNAs and 537 DEmRNAs. Afterwards, the cytoplasm ceRNA network was consisted of 537 DEmRNAs, 12 DEmiRNAs and 12 DElncRNAs. Such as, up-regulated LncRNA-HOX transcript antisense RNA (HOTAIR) was interacted with down-regulated has-miR-326 and has-miR-1. The successful construction of lncRNA-associated ceRNA network is helpful to better clarify the pathogenesis of CAD and provide potential peripheral blood biomarkers for CAD.

In-hospital and 1-year outcomes of patients without modifiable risk factors presenting with acute coronary syndrome undergoing PCI: a sex-stratified analysis

Abstract Background The standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking) are known to play a major role in the pathogenesis of coronary heart disease (CHD). Despite endeavors aiming at primary and secondary prevention of these risk factors, CHD has remained a leading cause of mortality and morbidity worldwide. A considerable proportion of patients admitted with acute coronary syndrome (ACS) have no SMuRFs, the outcomes of whom following percutaneous coronary intervention (PCI) are debated. Further, sex differences within this population have yet to be established. Purpose The present study aimed to evaluate the association between SMuRF-less status and post-PCI outcomes among patients with ACS. Further, we sought to determine possible sex differences in the post-PCI outcomes related to the SMuRF-less status. Methods This retrospective cohort study included 7847 patients with ACS who underwent PCI. The study outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACCE). The association between the absence of SMuRFs (SMuRF-less status) and outcomes among all the patients and each sex was assessed using logistic and Cox proportional hazard regressions. A separate landmark analysis with the landmark (cutoff) set at 30 days after the index procedure was performed as well. Models were adjusted for age, sex, body mass index, chronic obstructive pulmonary disease, cerebrovascular accident, previous myocardial infarction, estimated glomerular filtration rate, ejection fraction, and left main disease. Results Approximately 11% of the study population had none of the SMuRFs. The SMuRF-less and SMuRF+ groups aged 63.10 ±8.91 (85.1% males) and 62.53 ± 10.91 years (74.9% males), respectively. During 12.13 [11.99-12.36] months of follow-up, the followings were respective event numbers in the SMuRF-less and SMuRF+ groups: all-cause mortality: 35 (4.1%) and 273 (3.9%); MACCE: 99 (11.6%) and 898 (12.8%). All-cause mortality (adjusted-hazard ratio (HR): 1.01, 95%CI: 0.88-1.46, P: 0.731), and MACCE (adjusted-HR: 0.93, 95%CI:0.81-1.12, P: 0.412) did not differ between patients with and without SMuRFs (Figure 1). Sex-stratified analyses recapitulated similar outcomes between SMuRF+ and SMuRF-less men. In contrast, SMuRF-less women had significantly higher all-cause mortality (adjusted-HR:1.41, 95%CI: 1.02-3.21, P: 0.008) than SMuRF+ women (Figure 1). Notably, following landmark analyses, this significant association among women disappeared (adjusted-HR: 0.99, 95%CI: 0.41-2.59, P:0.991), implying that its significance stemmed, to some extent, from higher 30-day mortality (Figure 1,2). Conclusions Almost one in 10 patients with ACS who underwent PCI had no SMuRFs. The absence of SMuRFs did not confer any benefit in terms of in-hospital mortality, one-year mortality, and MACCE. Even worse, SMuRF-less women paradoxically had an excessive risk of one-year mortality.

Analysis of Correlation Between Coronary Heart Disease and Genetic Polymorphism Detected by Gold Magnetic Nanoparticles Chromatography.

It aimed to explore the correlation of Glu504Lys locus mutation of aldehyde dehydrogenase-2 (ALDH2) with coronary heart disease (CHD) based on gold magnetic nanoparticles (GMNPs) chromatography and amplification refractory mutation system-PCR (ARMS-PCR). 120 CHD patients admitted to the cardiovascular Department of Wenling First People's Hospital affiliated to Wenzhou Medical University from December 2020 to December 2021 were selected as Case group and 80 non-CHD patients admitted during the same period were selected as Ctrl group. The venous blood and indexes of Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Fasting Blood Glucose (FBS) were collected. The ARMS-PCR GMNPs chromatography based on ARMS-PCR and immunochromatography assay was adopted to detect gene polymorphism of ALDH2. Correlation between ALDH2 gene polymorphism and risk factors of CHD was analyzed via logistic regression. In contrast to Ctrl group, the genotypes of GG, GA, and AA in Case group were evidently different (P < 0.05), and the frequency of A allelic gene was obviously increased (P < 0.05). Under the dominant model, frequency of GA + AA genotype in Case group was remarkably higher in contrast to Ctrl group (P < 0.05). Under the recessive model, there was no obvious difference in genotype frequency between two groups. In contrast to Ctrl group, TC, LDL-C, and FBS in Case group were notably increased (P < 0.05), while HDL-C was notably decreased (P < 0.05). The distribution frequency of abnormal LDL-C, HDL-C, and FBS in Case group was notably higher in contrast to Ctrl group (P < 0.05). LDL-C and FBS had no obvious effect on the genotypes and frequency distribution of alleles in CHD patients. However, the frequency distribution of genotypes of GA and AA and A allelic gene in patients with abnormal HDL-C was notably lower in contrast to those with normal HDL-C (P < 0.05). Logistic regression analysis showed that abnormal HDC-C with A allelic gene were independent risk factors for CHD (P = 0.001, OR = 1.934). The gene polymorphism of Glu504Lys locus of ALDH2 was closely related to the pathogenesis of CHD, A allelic gene may be a susceptibility gene for CHD, and patients with abnormal HDC-C and carried A allelic gene had relatively higher incidence of CHD.

High dietary inflammatory index is associated with decreased plaque stability in patients with coronary heart disease

Coronary plaque stability is a key pathological mechanism of coronary heart disease (CHD). Inflammation is recognized as a key factor of coronary plaque stability. The dietary inflammatory index (DII) is calculated from 21 dietary nutrients to predict the inflammation potential of an individual's diet. We hypothesized that high DII may be associated with decreased coronary plaque stability in CHD patients; therefore, this study aimed to evaluate the association between DII and plaque stability in patients with CHD. This cross-sectional study included 314 patients with CHD. DII was calculated based on food frequency questionnaires. Plaque stability was measured with optical coherence tomography. The DII ranged from –1.41 to 3.04. After adjusting for confounding factors, higher DII scores were associated with unstable plaque characteristics including thin-capped fibroatheroma (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.78–7.29), macrophage infiltration (OR, 2.16; 95% CI, 1.01–4.61), and plaque rupture (OR, 3.55; 95% CI, 1.73–7.29). Mediation analyses revealed that DII was important mediator of the relationship between plaque stability and food intake including soybeans and nuts, fish and shrimp, eggs (P < .05). The present study confirmed that higher DII is significantly associated with decreased plaque stability in CHD patients, suggesting an important protective role of anti-inflammatory diets in the pathogenesis of CHD.

Association of Circulating Matrix Metalloproteinase-9 and the Risk of Coronary Heart Disease in Young Smokers

Introduction: Smoking causes cardiovascular risk which may alter the stability between the production and degradation of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is a zinc-containing endopeptidase that degrades the extracellular matrix and plays a vital role in tissue remodeling. As a result, elevated serum MMP-9 levels produced by smoking, particularly at young age, raise the risk of future CHD. So this study aims to find out the possible relationship between circulating MMP-9 and the risk of cardiovascular disease in young smokers. Methods: The study was conducted on smokers with CHD subjects attending cardiology and medicine OP of the SRM Medical College Hospital and research center Tamil Nadu, India. The study group was divided into three groups. Group 1 includes 120 healthy controls as nonsmokers, Group 2 includes 120 smokers with Coronary heart disease (CHD), and Group 3 includes 120 smokers with diabetes and CHD subjects in the age group of 20-55 years. Serum MMP-9, hs-CRP, and APO-E levels were measured using the ELISA method and the lipid level was measured enzymatically using AU480 automatic analyzer (back man coulter). Results: The mean serum MMP-9, hs-CRP, and APO-E levels were significantly higher in both groups (p&lt;0.05) when compared to controls. The study also shows a significant positive association between MMP-9 with hs-CRP, APO-E, smoking burden, and smoking intensity. Conclusion: The study concludes a significant association exists between cigarette smoking with MMP-9 and also relative exposure to circulating inflammation markers plays a potential role in the pathogenesis of CHD.