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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., Competing Interests: Declarations. Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics statement: This study was approved by the institutional ethics committee of the General Hospital of the Chinese People’s Liberation Army (PLA) (approval number S2021-522–02) on November 30th, 2021. The institutional ethics committee of the Chinese PLA General Hospital waived the need for written informed consent as deidentified data were used., (© 2024. The Author(s).)

This study aims to analyze the correlation between Systemic Inflammatory Response Index (SIRI) and the severity of coronary artery stenosis in patients with coronary heart disease (CHD). It also aims to assess the predictive value of SIRI for the severity of coronary artery stenosis. A total of 2990 patients who underwent coronary angiography were included in this study. The Gensini score was used to estimate the severity of coronary vascular lesions. The predictive ability of SIRI for CHD was evaluated using receiver operating characteristic (ROC) curves. Binary multivariate logistic regression analysis was used to predict the likelihood of CHD based on the SIRI index. The results showed that people with higher SIRI were more likely to have CHD (P < 0.001). After controlling for other risk factors, the highest quartile had a significantly higher incidence of coronary artery disease compared to the lowest quartile (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.73-3.92, P < 0.001). Furthermore, the Gensini score was significantly higher in the fourth quartile group (T4) compared to the first (T1) and second (T2) quartile groups (P < 0.001). Additionally, the SIRI was significantly higher in the group with severe coronary artery lesions compared to the mild and moderate groups (P < 0.001). The SIRI also showed a higher predictive ability for the extent of coronary lesions under the ROC curve compared to other commonly used markers, including platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001). Therefore, SIRI positively correlates with coronary artery stenosis in CHD patients, serving as an effective early screening marker for assessing stenosis severity.

Cellular senescence is an irreversible arrest of cell proliferation triggered by different stimuli, including DNA damage, telomere shortening and oncogenic stress. Senescent cells, by releasing the senescence-associated-secretory-phenotype (SASP), contribute to various diseases pathogenesis. Human atherosclerotic plaque contains cells with multiple markers of senescence that associate with disease severity. We characterized the frequency of senescent cTfh cells and genes expressions before and after treatment with Dasatinib in patients with different degrees of stenosis. Twelve high (≥50%), and twelve low (<50%) stenosis patients and six healthy controls were enrolled. The percentage of senescent CD3 + CD4 + CXCR5 + CD153 + CD57 + cells was significantly decreased in Dasatinib treated cells from individuals with low and high stenosis (P = 0.0007 and P = 0.0002, respectively). However, the frequency of total lymphocytes, CD3 + and CD4 + T cells were not significantly different between the groups before and after treatment. The expression levels of P53 (P = 0.0003 and P = 0.0001), P16 (P = 0.0005 and P = 0.0002), p21 (P = 0.0002 and P < 0.0001), SENEX (P = 0.0005 and P < 0.0001) and BCL-2 (P = 0.0005 and P = 0.0002) were decreased in PBMCs of low and high stenosis groups after treatment with Dasatinib, respectively. The percentage of senescent cTfh cells positively correlated with cholesterol (P = 0.034; r = 0.671), C-reactive protein (CRP) (P = 0.029; r = 0.707), Erythrocyte sedimentation rate (ESR) levels (P = 0.030; r = 0.598) and neutrophil counts (P = 0.021; r = 0.799) in patients with high stenosis. The decreased frequency of senescent cTfh cells and the expression levels of senescence genes after Dasatinib treatment in patients with atherosclerosis suggest a role for Dasatinib in partial clearance or rejuvenation of senescent cTfh cells, which may decrease inflammatory mediators and attenuate disease progression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Diabetes increases the risk of myocardial infarction (MI) by 2 to 3 folds. Tlymphocytes play a role in atherosclerosis, which is the main pathology behind MI. Cellular immune responses to beta-2 glycoprotein I (β2GPI) are shown in carotid atherosclerosis., Objective: To investigate the self-reactive, β2GPI-specific T-lymphocytes in patients with and without diabetes and atherosclerosis., Methods: Collectively, 164 subjects with and without diabetes that underwent coronary angiography were divided into four groups based on their diabetes status and coronary stenosis. Group I=Diabetic with ≥50% stenosis: A+D+ (n=66); Group II=Non-diabetic with ≥50% stenosis, A+D- (n=39); Group III=Diabetic with <50% stenosis: A-D+ (n=28); and Group IV=Non-diabetic with <50% stenosis: AD- (n=31). All groups were evaluated for anti-β2GPI IgG antibody by ELISA method. Then, PBMCs were isolated from 18 subjects and were stimulated with β2GPI-derived peptides to assess their proliferation in accordance with their HLA-DRB1 alleles., Results: Mean β2GPI IgG levels were higher in groups with ≥50% stenosis (A+) compared to those with <50% stenosis (A-), (P=0.02). The co-presence of diabetes in A+ individuals increased mean β2GPI-specific IgG. Auto-reactive β2GPI-specific T cells were detected in the repertoire of T-lymphocytes in all groups. β2GPI-peptides showed promiscuous restriction by various HLADRB1., Conclusion: β2GPI is the target of cellular and humoral immune responses in patients with atherosclerosis. Since the T cell responses but not antibodies were detectable in A-D+ and A-D- groups, it is reasonable to assume that cellular responses preceded the humoral responses. Post-translation modifications of β2GPI under oxidative and glycemic stresses may have increased the IgG levels in patients with diabetes. Finally, identification of antigens that trigger immuno-pathogenesis in atherosclerosis and diabetes may help the development of immunomodulation methods to prevent or treat these debilitating diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: The study aimed to investigate and compare the predictive capacity of a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to determine a hemodynamically significant coronary artery stenosis assessed by fractional flow reserve (FFR). Patients & methods: A total of 207 chronic coronary syndrome patients with FFR measurement were enrolled in the study. NLR, PLR and SII levels were calculated. Results: The cut-off value of the SII (620) was associated with 78.4% sensitivity and 64.0% specificity to predict a hemodynamically significant stenosis. SII level independently predicted FFR ≤0.80. Conclusion: SII is an independent predictor of functionally significant coronary stenosis detected by FFR in chronic coronary syndrome patients. SII levels can predict hemodynamically severe obstruction better than NLR and PLR.

Aims: Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features., Methods: Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software., Results: For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in CHD patients compared to control group; 2) the hypomethylation level of one specific fragment of 161bp (+616/+777) positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups evaluated and was predictive for disease severity., Conclusions: Reduced levels of circulating HLA-G molecules could derive from epigenetic marks. Epigenetics phenomena induce hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive non critical stenosis vs coronary stenosis individuals., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: The complement system plays an important role in the development of acute coronary syndrome (ACS). Complement C1q is an important initial component of the classical complement pathway and closely related to many chronic inflammatory diseases, including atherosclerosis (AS). We aimed to determine whether there was association between serum complement C1q and the severity of coronary stenosis., Subjects and Methods: 320 patients who underwent coronary arteriography (CAG) were stratified into non-ACS group (control group, n = 74), unstable angina group (UA group, n = 197) and acute myocardial infarction group (AMI group, n = 49) according to the severity of coronary stenosis and clinical manifestations. The severity of coronary stenosis was represented in Gensini score, and serum complement C1q level was compared using immunity transmission turbidity among three groups., Results: The level of complement C1q in AMI group was lower significantly than control group and UA group (P < 0.05), but there was no correlation between serum complement C1q and Gensini score (β=-0.086, P = 0.125). In nitrate-taking patients, serum complement C1q had a negative association with Gensini score (r=-0.275, P = 0.001), and in non-smokers, there was also a negative correlation (β=-0.159, P = 0.036). After calibrating smoking, drinking or statins, the serum complement C1q levels of control group, UA group and AMI group decreased in sequence (P <  0.05). Logistic regression analysis showed that the decreasing of serum complement C1q was an unfavorable factor for acute myocardial infarction (OR=0.984, 95 %CI=0.972∼0.997, P = 0.015) and for ACS (OR=0.984, 95 %CI=0.971∼0.984, P = 0.025) in drinking patients. Regrettably, ROC curve suggested that the accuracy in diagnosing coronary atherosclerotic heart disease by serum complement C1q was low (AUC=0.568, 95 %CI= 0.492-0.644, P = 0.076, sensitivity 73.6 %, specificity 58.1 %)., Conclusion: Serum complement C1q in ACS patients, in particular AMI patients, showed lower level. This finding suggests further decrease of complement C1q level in ACS patients may be a contributory factor to instability or rupture of atherosclerotic plaques. Combined with other clinical indicators, it can be helpful to predict the risk and severity of coronary stenosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Kawasaki disease (KD) patients could develop coronary artery lesion (CAL) which threatens children's life. A previous study identified KD biomarker miRNAs that could discriminate KD patients from febrile non-KD patients. We wonder whether these KD prediction biomarkers could be further applied to predict CAL formation in KD patients., Methods: To examine this hypothesis, we conducted a meta-analysis, miRNA mimic transfection, in vitro cell model and microarray assays., Results: We first showed that miR-182-5p and miR-183-5p kept higher levels in the KD patients with CAL than those without CAL (p < .05). Further machine learning alignment confirmed that CAL formation could be predicted, with an auROC value of 0.86. We further treated neutrophil cells with miR-182-5p mimic, followed by in vitro transendotherial migration assay. As a result, miR-182-5p overexpression significantly (p < .05) enhanced neutrophil cells to infiltrate the endothelial layer composed of human coronary artery endothelium cells. Further microarray assay and pathway enrichment analysis showed that the genes activated with miR-182-5p overexpression were significantly enriched in the leukocyte transendothelial migration pathway (kegg&#95;pathway&#95;194, p < .05)., Conclusion: Therefore, our study suggested that miR-182-5p enhanced in vitro leukocyte infiltration by activating the leukocyte transendothelial migration pathway in CAL formation in KD., (© 2019 Kaohsiung Veterans General Hospital / Kaohsiung Chang Gung Memorial Hospital. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

The effect of 20 fatty acids in erythrocyte cell membranes on the extent of inflammatory response and cell oxidative stress was evaluated using multidimensional statistical data analysis in 54 patients suffering from ischemic heart disease undergoing percutaneous coronary intervention with coronary stent implantation using multidimensional statistical data analysis. A systemic inflammatory response was indicated by an increase of C-reactive protein (CRP), serum amyloid A (SAA) and ceruloplasmin 48 h after stent implantation and by an increase of interleukin-6 (IL-6) 24 h after intervention. The increase of malondialdehyde (MDA) after 48 h was used as a marker of cell damage by oxidative stress. Multiple linear regression revealed statistically significant relationships between concentration of some fatty acids and the magnitude of inflammatory response, or oxidative stress, after stent implantation. The most significant relationship with an increase of plasma CRP was found for myristic acid and, to a lesser extent, for oleic acid. Trans octadecenoic acid, and to a lesser extent palmitooleic and nervonic fatty acids were found in inverse correlation with the CRP increase. The increase of IL-6 showed a statistically significant correlation with myristic acid, to a lesser extent with cis-9-eicosenoic acid and to the least extent with docosahexaenoic acid, inversely with pentadecanoic, γ-linolenic and stearic acids. An increase of oxidative stress (MDA) significantly correlated only with γ-linolenic acid. Other studied markers of inflammatory response to coronary stenting were SAA and ceruloplasmin (Cp). Statistical evaluation revealed that SAA and Cp are not suitable markers for assessment relationships between inflammation and erythrocyte membrane fatty acids., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Inflammatory cells in atherosclerotic plaque exclusively originate from hematopoietic stem/progenitor cells (HSPCs). In this study, we investigated whether circulating HSPCs frequency related to coronary stenosis in patients with coronary heart disease (CHD). Coronary angiography was performed in 468 participants who were recruited at Cardiology Centre in LuHe Hospital from March 2016 to May 2017. Among these subjects, 344 underwent echocardiography. Mononuclear cells isolated from peripheral blood were stained with an antibody cocktail containing anti-human CD34, anti-human lineage, anti-human CD38, and anti-human CD45RA. Lineage - CD38 - CD45RA dim CD34 + HSPCs were quantified by flow cytometry. CHD was defined as coronary stenosis ≥50% and the extent of CHD was further categorised by coronary stenosis ≥70%. A p < 0.0031 was regarded statistically significant by the Bonferroni correction. Circulating HSPCs frequency was 1.8-fold higher in CHD patients than non-CHD participants (p = 0.047). Multivariate-adjusted logistic analysis demonstrated that HSPCs was the only marker that was associated with the odds ratio of having mild vs. severe coronary stenosis (2.08 (95% CI, 1.35-3.21), p = 0.0009). Left ventricular ejection fraction was inversely correlated with HSPCs frequency and CRP in CHD patients (p < 0.05 for both). In conclusion, HSPCs frequency in circulation is intimately related to coronary stenoses in CHD patients.

Background and Aims: Periodontitis, a common polymicrobial inflammatory disease in the tooth supporting tissues, is a risk factor for coronary artery disease. One of the proposed underlying mechanisms is the systemic immune response to periodontal infection. We studied how serum antibodies against seven periodontal pathogens and their subgingival levels associate with each other, periodontitis, and coronary artery disease., Methods: The Parogene cohort included 505 Finnish patients (mean age 63 y) who underwent coronary angiography, and clinical and radiographic oral examinations. Coronary diagnosis was defined as no significant coronary artery disease (<50% stenosis, n = 152), stable coronary artery disease (≥50% stenosis, n = 184) and acute coronary syndrome (n = 169). Levels of subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Tannerella forsythia, Campylobacter rectus, and Fusobacterium nucleatum were determined by checkerboard DNA-DNA hybridization. Serum antibody (IgA/IgG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Aggregate IgA/IgG burdens were calculated by summing and standardizing the serum antibody levels., Results: Patients with active periodontitis were characterized by higher levels of subgingival bacteria and corresponding IgA/IgG response. Quartiles 2-4 of serum IgA/IgG burden indicated higher risk for acute coronary syndrome (OR 1.84, 95%CI 1.01-3.35 for IgA; OR 1.87, 95%CI 1.01-3.46 for IgG) independently of established cardiovascular risk factors, body mass index, number of teeth, subgingival bacterial levels and periodontal diagnosis., Conclusions: Our findings support the hypothesis that the association between periodontitis and cardiovascular diseases is partly mediated by the immunologic response for periodontal pathogens., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Circulating leukocyte subtypes and monocyte subsets are independent predictors of cardiovascular events. We hypothesized that an increased leukocyte subtype would predict severe coronary stenosis and extensive plaque involvement. We retrospectively analyzed clinical, laboratory, and coronary CT data in a total of 588 asymptomatic adults (69% men; mean age, 57 ± 9 years) undergoing a general health check-up. Intermediate CD14 ++ CD16 + monocyte count had the strongest association with mixed and calcified plaque scores, whereas the numbers of neutrophils and classical CD14 ++ CD16 - monocytes were significantly associated with non-calcified plaque score. Only high CD14 ++ CD16 + monocyte count (>12 cells/μL) significantly predicted extensive plaque involvement [odds ratio 3.16 (95% confidence interval 1.84-5.43), P < 0.001; quartile 4 vs. 1-3] and severe coronary stenosis [3.67 (1.84-7.33), P < 0.001; quartile 4 vs. 1-3] after adjustments for Framingham Risk Score (FRS), metabolic syndrome, and C-reactive protein. The CD14 ++ CD16 + monocyte count, when added to FRS, significantly reclassified 30.4 and 26.7% of the overall and 50.2 and 36.2% of the intermediate-risk population (FRS 6-20%) for predicting extensive plaque involvement and severe coronary stenosis, respectively. Thus, in asymptomatic individuals, intermediate CD14 ++ CD16 + monocyte could independently predict severe CAD and improve risk stratification.

Background: The macrophage polarization is proposed to be involved in initial events and remodeling of atherosclerosis plaques. Mannose receptor, C type 1 (MRC1) is a trans-membrane glycoprotein participating in phagocytosis and, is highly expressed in the M2 macrophages., Objective: The aim of this study was to investigate the effects of sdLDL (small dense LDL) on the MRC1 gene expression level and secretion of histamine in the differentiated M2 macrophages from monocytes of patients with coronary artery stenosis and healthy subjects., Method: The monocytes were isolated from healthy subjects (< 5% stenosis) and patients (> 70% stenosis, SVD (Single Vessel Disease), 2VD (Two-Vessel Disease) and 3VD (Three-Vessel Disease)) by RosetteSep kit and, were differentiated into M2 macrophages by macrophage colonystimulating factor (M-CSF). The sdLDL particles were obtained by PEG-combined precipitation method. The MRC1 gene expression and histamine levels were measured by RT-qPCR and ELISA techniques, respectively., Results: The MRC1 gene expression level was significantly increased in M2 macrophages of healthy subjects (P=0.05) while it reduced in SVD (P=0.05), 2VD (P=0.01) and 3VD (P=0.9) patients after treatment with sdLDL. The histamine value secreted from M2 macrophages (7-day) was higher (>3-fold, P=0.02) in patients as compared to healthy controls., Conclusion: The results showed that the sdLDL particles reduce the MRC1 gene expression levels in the differentiated M2 macrophages from patients with coronary artery disease. Furthermore, they had high inflammatory capacity for the secretion of histamine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

We evaluated immune activation and coronary artery plaque in young adults with human immunodeficiency virus acquired in early life (n = 31). Coronary plaque was positively associated with lipids, immune activation marker %CD8+CD38+DR+ and E-selectin, a marker of endothelial inflammation. Immune activation and endothelial inflammation may drive coronary plaque formation during the early stages of atherosclerosis in the context of chronic human immunodeficiency virus., Competing Interests: The authors have no financial conflicts of interest to report in relationship to this research or manuscript.

A 76-year-old woman with multiple coronary risk factors was admitted to our hospital because of episodes of new-onset chest pain that had begun 3 days previously. She underwent percutaneous coronary intervention (PCI) for severe stenoses in the two high lateral (HL) branches. Intravascular ultrasound (IVUS) revealed massive stenotic lesions in the HL branches and tumorous nonstenotic lesions in the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). iMAP™, optical coherence tomography (OCT), and coronary computed tomography angiography (CCTA) were performed. iMAP depicted fibrosis in the vessel (green areas) and nonfibrotic tissue change suggestive of inflammation outside the vessel (yellow/red areas). OCT revealed high-intensity homogenous intimal hyperplasia with superficial calcification, and CCTA showed massive periarterial soft lesions in the HL, LAD, and LCx. The serum IgG4 level was high at 252-427 mg/dL (8 measurements) (reference range, 4.8-105.0 mg/dL). We suspected IgG4-related coronary periarteritis on the basis of the comprehensive diagnostic criteria as a possible diagnosis. The clinical course was good after initial and subsequent PCIs for both the HL stenoses and the progressing LCx stenosis, and there was no recurrence of angina pectoris thereafter. Steroids were not administered because the massive lesions did not enlarge during the 16 months of follow-up. iMAP was able to evaluate the tissue characteristics of tumorous lesions in the stenosed HL branches and the nonstenotic LAD and LCx in a patient with an elevated level of IgG4.

Background: Heightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study., Methods: We performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors., Results: Levels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque., Conclusions: sCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Low anti-phosphorylcholine (PC) IgM plasma levels have been associated with increased incidence of adverse events in coronary artery disease (CAD). The underlying mechanisms are unclear. We hypothesized that atheroprotection mediated by anti-PC IgM antibodies is associated with reduced vascular remodeling and therefore tested whether anti-PC IgM plasma levels independently predict vascular remodeling. In a prospective cross-sectional study, anti-PC IgM plasma levels were measured in 175 consecutive patients with suspected CAD undergoing cardiac computed tomography angiography. Plaque morphology was thoroughly analyzed. Vascular remodeling was defined by a change in the vessel diameter at the plaque site in comparison to the reference segment proximal to the lesion (reference diameter) of ≥10%. Mean age of the patients was 64.8 ± 10.7 years, 48.6% were female. In 98 patients CAD was diagnosed, 57 (58.2%) of which displayed non-obstructive CAD (stenosis <50%), whereas 41 (41.8%) exhibited obstructive CAD (stenosis ≥50%). In 34 of 98 (34.7%) CAD patients vascular remodeling was present. Mean anti-PC IgM levels did not differ between patients with and without CAD (70.8 ± 52.7 vs. 69.1 ± 55.1 U/mL). However, anti-PC IgM levels were significantly lower in CAD patients compared to those without vascular remodeling (46.6 ± 31.6 vs. 73.3 ± 58.5 U/mL, P = 0.024). Using multivariate logistic regression, anti-PC IgM plasma levels independently predicted coronary vascular remodeling (HR 0.322, 95% confidence interval 0.121-0.856, P = 0.023). In conclusion, low anti-PC IgM levels are independently associated with coronary vascular remodeling. These findings may represent the link between in vitro studies demonstrating atheroprotective effects of anti-PC IgM and clinical data demonstrating that low anti-PC IgM levels are associated with adverse outcome in CAD patients.

This study aimed to investigate the relation between the neutrophil-to-lymphocyte ratio (NLR) and the severity of coronary artery stenosis. A total of 219 patients were included in the study, comprising 51 coronary artery atherosclerosis (CAC) patients, 92 stable angina pectoris (SAP) patients, and 76 acute coronary syndrome (ACS) patients. Based on the results of coronary angiography, all patients were divided into two groups according to the Gensini scores: the low-score group (N = 142) and the high-score group (N = 77). The NLR was computed from the ratio of neutrophils and lymphocytes from the complete blood count. The association between the NLR and severity of coronary artery disease was assessed using correlation analysis and logistic regression. The NLR was higher in ACS patients than in SAP and CAC patients (P < 0.05). In addition, the NLR was higher in the high-score group than in the low-score group (P < 0.05). Correlation analysis showed that the NLR was significantly correlated with the Gensini score. After multivariate analysis, high NLRs were independent predictors of high Gensini scores, together with age and high-density lipoprotein. A cutoff NLR of 2.385 predicted high Gensini scores with a sensitivity and specificity of 64 and 63%, respectively. The study suggests that the NLR is an independent predictor of coronary heart disease that may be useful for predicting the severity of coronary artery stenosis.

Coronary artery disease (CAD), as a lipid-driven and inflammation-driven disease, has threatened thousands of patients' lives. Toll-like receptors, the most characterized innate immune receptors, have recently been demonstrated to play a key role in coronary artery disease, particularly Toll-like receptor (TLR) 3 and TLR4. We examined TLR3, TLR4, and associated inflammatory factors expression in monocytes and their signaling pathway proteins in patients with varying degrees of coronary artery atherosclerosis [group S (single diseased vessel), n = 36; group D (double diseased vessels), n = 36; group T (three diseased vessels), n = 33 compared with controls (n = 35)]. In mononuclear cells, TLR3 mRNA and protein, and IRF-3 were significantly down-regulated as the coronary arteries stenosis number increased. However, TLR4 mRNA and protein, and MyD88 were significantly increased in patients with coronary artery stenosis compared with controls, and were associated with the number of stenoses. In serum, there was significant up-regulation in TNF-α, IL-8, and MCP-1 and obvious down-regulation in INF-β and IP-10 with severity of CAD. This study demonstrates differential expression of TLR3 and TLR4 at both the mRNA and protein level in both mononuclear cells and downstream serum readouts of patients with CAD compared with the control. The expression of TLR4 and TLR3 closely correlated with the severity of coronary artery disease as reflected by the number of coronary artery stenoses. TLR3 and TLR4 have the potential to be a clinically useful biomarker of cardiovascular risk.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by multiorgan fibrosis with IgG4-producing plasma cells, increased IgG4 serum concentration, and responsiveness to steroid therapy. Involvement of the pancreas, salivary glands, orbit, aorta, and other sites has been well documented in the literature; however, there have been limited reports of cases involving the coronary arteries. We report the case of a 53-year-old Hispanic man who was brought to the emergency center and diagnosed with sudden cardiac death. Autopsy was subsequently performed, revealing multiorgan involvement by IgG4-RD, including involvement of the coronary arteries. The inflammation and fibrosis, in combination with concomitant atherosclerotic disease, resulted in severe stenosis of the coronary arteries. Two of the coronary arteries were further occluded by thrombosis. These factors led to cardiac hypoperfusion, myocardial infarction and, ultimately, sudden cardiac death. Fatal involvement of the coronary arteries has not been previously reported, raising a new concern for a severe complication of IgG4-RD.

Objective: The SYNTAX Score was recently developed to characterize the coronary vasculature with respect to the number of lesion's location, complexity, and functional impact and it is a quantitative scoring system to assist with patient selection for optimal revascularization strategy between percutaneous coronary intervention (PCI) and coronary artery by-pass surgery (CABG). b2-glycoprotein I (b2GPI), a plasma protein that binds cardiolipin, acts as a modulator of platelet aggregation and coagulation. Antibodies to b2GPI may have a role in atherosclerosis by inducing endothelial cell activation. We investigated the relationship between anti beta 2 GPI and severity of coronary artery stenosis by calculating the SYNTAX Score among patients undergoing CABG surgery., Patients and Methods: We prospectively investigate 612 patients who undergo elective coronary angiography between September 2012 and June 2013. Patients were evaluated for blood chemistry and anti-b2GPI IgA, IgM and IgG. Ninety seven patients with complete biochemical analysis including anti Beta 2 GPI antibodies and undergone CABG have been enrolled in this study. We divided patients in to 2 groups according to the SYNTAX scores. Group 1 included 48 patients with low SYNTAX scores (<23) and group 2 included 49 patients with intermediate and high SYNTAX scores (>23)., Results: There was significant correlation between elevated anti b2GPI IgG levels and higher SYNTAX score which indicate advanced and complex CAD. In this study, lesion complexity increased progressively with increasing anti-b2GPI-IgG type of antibody levels. According to this findings, anti-b2GPI-IgG is a strong predictor of higher SYNTAX score., Conclusions: In addition to the traditional risk factors for atherosclerosis, the proinflammatory and procoagulant activities of antiphospholipid antibodies appear to be important risk factors for atherosclerotic occlusive disease.

We evaluated the association between inflammatory markers and coronary artery plaque assessed by 64-slice multidetector computed tomography. Coronary computed tomography angiography was performed in patients with chest discomfort suggestive of coronary artery disease (CAD). Individuals with an acute coronary syndrome were excluded from the study. Coronary plaque morphology, the number of artery segments exhibiting plaque, and the number of vessels with >50% stenosis were evaluated. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. Among the 178 patients studied (age 65 ± 10 years; 70% men), 125 were diagnosed with CAD. Hs-CRP and IL-6 concentrations were significantly higher in patients with CAD than in patients without (2.73 ± 4.7 vs. 1.32 ± 2.6 mg/L, P = 0.018, and 3.06 ± 3.3 vs. 2.19 ± 2.4 pg/mL, P = 0.036). The IL-6 level was high in patients with predominantly calcified plaque, and was significantly higher in patients with 4-9 plaque segments than in those with no or 1-3 plaque segments (4.07 ± 5.3 vs. 2.19 ± 2.4 pg/mL and 2.43 ± 2.0 pg/mL, respectively, P = 0.025). The number of stenotic vessels was not significantly related to inflammatory markers. Multivariate logistic analysis revealed that plasma levels of hs-CRP but not IL-6 were associated with the presence of coronary plaque with calcification (OR 3.37, P = 0.026). This study supports the usefulness of inflammatory markers for the evaluation of coronary plaque in patients with stable CAD.

Objectives: This study sought to compare the efficacy and safety results after coronary implantation of a combined sirolimus-eluting CD34 antibody coated Combo stent (OrbusNeich Medical, Ft. Lauderdale, Florida) with the paclitaxel-eluting Taxus Liberté stent (PES) (Boston Scientific, Natick, Massachusetts). This report summarizes the first-in-man randomized, controlled multicenter REMEDEE trial (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) angiographic, intravascular ultrasound, and clinical results up to 12 months., Background: Drug-eluting stents have limited restenosis and reintervention but are complicated by especially late and very late stent thrombosis and accelerated neoatherosclerosis. Alternative or adjunct technologies should address these limitations., Methods: One hundred eighty-three patients with de novo native coronary artery stenoses were randomized 2:1 to Combo stent or PES implantation. The primary endpoint is the angiographic in-stent late lumen loss at 9 months, which was tested for noninferiority between the 2 stent groups. Secondary endpoints include the occurrence of major adverse cardiac events., Results: The Combo stent was found to be noninferior to the PES in 9-month angiographic in-stent late lumen loss with 0.39 ± 0.45 mm versus 0.44 ± 0.56 mm (pnoninferiority = 0.0012). At 12 months, the occurrence of major adverse cardiac events was 8.9% in the Combo group and 10.2% in the PES group (p = 0.80) with no difference in mortality, occurrence of myocardial infarction, or target lesion revascularization. No stent thrombosis was reported in either group., Conclusions: In the REMEDEE trial the Combo stent has shown to be effective by meeting the primary noninferiority angiographic endpoint and safe, with an overall low rate of clinical events in both stent groups, including no stent thrombosis up to 12 months., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

To explore the role of the IL-23/IL-17 axis in the relationship between periodontitis and coronary heart disease (CHD), 97 subjects were recruited and divided into four groups: (1) CHD + periodontitis, (2) CHD, (3) periodontitus alone, and (4) healthy. The demographic characteristics and periodontal status of all subjects were recorded, and the serum levels of IL-23/IL-17 were detected by enzyme-linked immunoabsorbent assay. Results showed that the serum levels of IL-23/IL-17 in groups 1, 2, and 3 were higher compared with group 4. Group 1 manifested the highest level of serum IL-23/IL-17. A significant positive correlation between IL-23 and IL-17 levels was seen in the three patients groups; groups 1 and 3 also had significant positive correlations with probing depth and attachment loss. The results indicate that there may be an association between periodontitis and CHD, and the IL-23/IL-17 axis may play an important role in the pathologic process of both diseases.

Objectives: An increased circulating monocyte count has been found to be related to good collateral development in patients with stable coronary artery disease. Our aim in this study was to determine any possible relationship between the levels of circulating monocyte subsets and coronary collateral development., Methods: Patients who had greater than 95% stenosis of at least one major coronary artery in their first coronary angiogram were included consecutively in this study. Collateral development was graded as good and poor according to the Cohen-Rentrop method. Blood samples were subjected to cytometric analysis for the determination of monocyte subsets, CD14++CD16- and CD14+CD16+ monocytes., Results: Out of 105 patients, 55 had good and 50 had poor coronary collateral development. When the baseline characteristics were compared, the monocyte count was significantly higher in the good collateral group (517±151 vs. 396±109/mm3, P<0.001). Cytometric analysis indicated that CD14++CD16- levels were significantly higher in the good collateral group (422±147 vs. 298±105/mm3, P<0.001). CD14+CD16+ cells did not differ between groups (80±29 vs. 84±29/mm3, P=0.41). When multivariate analysis was performed, increased CD14++CD16- levels were still significantly associated with good collateral development [odds ratio: 1.009 (1.005-1.014), P<0.001]., Conclusion: Our present results are the first to show a significant association between increased circulating CD14++CD16- monocyte levels and good coronary collateral development. Further studies are needed to better understand the relationship between different subsets of monocytes and collateralization.

Objective: We assessed the 1-year clinical outcome in a large cohort of unselected patients treated with an endothelial progenitor cell (EPC) capturing coronary stent., Background: The novel EPC capturing stent is coated with CD34+ antibodies that bind circulating EPCs to the stent surface, thereby accelerating endothelialization of the stent struts; it is hypothesized that this may prevent restenosis and stent thrombosis., Methods: A total of 405 unselected patients were treated percutaneously with the EPC capturing stent. The majority of patients had complex lesions with an estimated high risk of restenosis., Results: The primary endpoint defined as the composite of cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) at 1-year was 13.3%, mainly attributable to TLR which was 10.9%. The occurrence of definite and probable ST was low, 0.5 and 0.7%, respectively. Based on the risk of restenosis, in patients with an estimated high risk of restenosis (n = 249), the composite primary endpoint was 16.1% versus 9.0% in patients with an estimated low risk (n = 155). Moreover, the 1 year clinical outcomes in diabetic patient compared well with the nondiabetic patients., Conclusion: In this single-center study, the 1-year clinical follow-up in a "real-world" population treated with the EPC capturing stent showed good results. Currently, large randomized studies are conducted to evaluate the long-term safety and efficacy of this stent., (Copyright © 2011 Wiley-Liss, Inc.)

Aims: Patients with type 2 diabetes (T2DM) have a high restenosis rate after percutaneous coronary intervention (PCI). This study investigated whether markers of inflammation and the adipo-insular axis associated with T2DM and poor metabolic control were able to predict restenosis after PCI in T2DM patients., Methods and Results: The predictive value of traditional and non-traditional risk markers, including IL-1β, IL-6, TNF-α, hsCRP, interferon gamma, leptin, IGF-I, insulin, proinsulin and NT-proBNP, was investigated in 82 patients with T2DM. A re-angiography 6 months after the index percutaneous coronary intervention (PCI) revealed that 43% of the patients had a restenosis. In a multiple regression analysis, the only independent predictors of restenosis were fasting glucose before the PCI and previous myocardial infarction (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.92; p = 0.015 and OR 8.00, 95% CI 2.49-25.67; p ≤ 0.001, respectively). None of the other markers remained as significant predictors., Conclusion: Fasting glucose prior to the PCI was an independent predictor of restenosis in patients with T2DM while analyses of a variety of markers related to inflammation and the adipo-insular axis did not add any further information.

We assessed the changes in serum antiheat shock protein (HSP)-27 antibody and high-sensitivity C-reactive protein (hsCRP) levels, following the placement of a drug-eluting stent (DES) or bare-metal stent (BMS) in patients with stable coronary artery disease. Either a BMS or DES was implanted in 137 patients (82 BMS; 55 DES). Anti-HSP27 and hsCRP levels were measured 24 hours before and 24 hours after stenting. Median hsCRP serum levels increased significantly to 60.78 (10.13-84.87) and 77.80 (50.00-84.84) mg/L for BMS and DES groups (P = .006 and P = .000, respectively); this increase did not differ significantly between the 2 groups. Median anti-HSP27 antibody levels decreased to 0.26 (0.17-0.49) and 0.21 (0.16-0.29) absorbency units in BMS and DES groups (P = .045 and P = < 0.001, respectively). The changes in anti-HSP27 antibody titers were significant between the 2 groups (P = .015). Bare-metal stent and DES differ in stimulation of immune rather than inflammatory responses. Less stent restenosis after DES compared with BMS implantation could, in part, be attributed to differences in immune responses.

Aim: To study association between the level of antibodies to oxidized low-density lipoproteins (anti-OLDL) and the extent of coronary stenosis (CS) in patients with coronary heart disease (CHD)., Material and Methods: Sixty CHD patients were examined for titer of anti-OLDL, levels of total cholesterol (TC), LDLP cholesterol, HDLP cholesterol, triglycerides. Selective coronarography (SC) was made on demand., Results: Elevated titer of anti-OLDL was found only in 12 examinees. It was significantly lower in CHD women than in men. No significant differences by anti-OLDL were found in CHD patients with and without significant risk factors. SC registered in all CHD examinees local stenosis of different severity. Stenosis in 3 coronary arteries was detected in 31 cases, in 2 coronary arteries--in 14, in 1 coronary artery--in 15 patients, most frequently the affection was located in the diagonal branch of the left coronary artery. Stenosis of the left coronary artery trunk was diagnosed in one case. The correlation analysis revealed a strongly significant positive correlation between content of anti-OLDL and the degree of CS., Conclusion: The level of anti-OLDL in CHD patients directly correlates with the degree of CS and is a marker of coronary atherosclerosis severity.

Background: The relationship between autoantibodies against human oxidized low-density lipoprotein (anti-oxLDL) and the progression of atherosclerotic diseases is unclear. This study aimed to investigate the association between serum anti-oxLDL titers and the severity and extent of coronary stenotic lesions., Methods: We measured the titers of IgG anti-oxLDL by enzyme-linked immunosorbent assay (ELISA) in 154 consecutive patients undergoing coronary angiography for suspected coronary heart disease (CHD). The severity and extent of coronary stenotic lesions were evaluated on coronary angiography findings by Gensini score., Results: The anti-oxLDL titers were significantly lower in 117 patients with CHD than those in 37 controls (p<0.01). The serum anti-oxLDL titers were significantly correlated to serum levels of globulin (r = 0.405), conjugated bilirubin (r = 0.280), high-density lipoprotein (HDL) cholesterol (r = 0.238), homeostatic model assessment for insulin resistance (HOMA-IR) (r = -0.267), high sensitivity C-reactive protein (hs-CRP) (r = -0.230), triglyceride (r = -0.207), advanced glycation end products (AGEs) (r = -0.200), and malondialdehyde (r = -0.165). However, only HDL cholesterol and AGEs remained independent predictors of the anti-oxLDL titers after adjusting for confounders. Multivariate regression analysis showed that the anti-oxLDL titers, as well as serum levels of hs-CRP, fasting glucose, and albumin, were significantly associated with Gensini scores., Conclusions: Titers of anti-oxLDL are inversely associated with complicated proatherogenic metabolic risk factors, and the severity of coronary stenotic lesions calculated by Gensini scores, supporting a protective role for anti-oxLDL against the progression of atherosclerosis.

Humoral immune responses to mismatched donor human leukocyte antigen (HLA) and major histocompatibility complex (MHC) class I-related chain A (MICA) have been reported to contribute to immunopathogenesis of antibody-mediated rejection (AMR) in the early period and cardiac allograft vasculopathy (CAV) in the late period after cardiac transplantation (HTx). The goal of this study is to define the roles of donor-specific antibodies (DSA) and anti-MICA in AMR and CAV. A total of 95 post-HTx recipients were enrolled; 43 patients in the early period (≤ 12 months post-HTx) and 52 patients in the late period (>12 months post-HTx). Development of DSA and anti-MICA were serially monitored using Luminex. Development of DSA (AMR+: n = 6/8.75%, AMR-: n = 4/35.11%, p = 0.009) and anti-MICA (AMR+: n = 5/8.63%, AMR-: n = 4/35.11%, p = 0.002) was significantly associated with AMR. AMR+DSA+ patients demonstrated increased anti-MICA levels compared with AMR+DSA- patients (p=0.01). Serial monitoring revealed DSA (2.7 ± 1.4 months) preceded development of anti-MICA (6.5 ± 2.1 months) in recipients diagnosed with AMR at 8.3 ± 2.5 months post-HTx. Development of DSA (CAV+: n = 8/12.67%, CAV-: n = 5/40.13%, p = 0.004) and anti-MICA (CAV+: n = 9/12.75%, CAV-: n = 5/40.13%, p = 0.001) was significantly associated with CAV. CAV+DSA+ patients demonstrated increased anti-MICA levels compared with CAV+DSA- patients (p = 0.01). Antibodies to HLA are associated with and precede development of anti-MICA in AMR and CAV. Therefore, DSA and anti-MICA can be used as noninvasive markers for monitoring AMR and CAV., (Copyright © 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Interleukin (IL)-18 is a proinflammatory cytokine that is present in chronically inflamed tissues; IL-18 was positively associated with periodontitis and coronary artery disease (CAD). CXC ligand (CXCL) 16, a recently discovered chemokine, was identified in atherosclerotic lesions; its role in periodontal disease is largely unknown. This research study correlates periodontal parameters with systemic levels of IL-18 and CXCL16., Methods: Fifty-one patients who presented for clinically indicated coronary angiography received full-mouth periodontal examinations. The periodontal status of patients was defined using frequency distributions of probing depth (PD), clinical attachment loss (AL), and bleeding on probing (BOP). Blood samples were collected during cardiac catheterization, and plasma levels of IL-18 and CXCL16 were analyzed. The severity of CAD was determined by the presence and extent of coronary artery stenosis. Correlations between periodontal parameters, levels of inflammatory mediators, and CAD status were analyzed., Results: The extent of BOP exhibited a significant positive correlation with IL-18 in the Spearman rank correlation analysis (P = 0.039), which indicated a correlation between periodontal inflammation and systemic IL-18 levels. When multiple regression analysis was performed, the extent of clinical AL > or =3 mm (P = 0.045) and > or =5 mm (P = 0.024) exhibited an association with IL-18, whereas CXCL16 was associated with clinical AL > or =5 mm (P = 0.040) and PD > or =7 mm (P = 0.047)., Conclusion: A significant correlation is identified between periodontitis and systemic levels of IL-18 and CXCL16 in patients undergoing diagnostic coronary angiography.

Objective: To determine the relationship between the number,phenotype and functional status of dendritic cells (DCs) and coronary collateral circulation (CCC) in coronary heart disease (CHD)., Methods: Forty patients with severe coronary stenosis were recruited and divided into a CCC formation group (Group A, n=22) and a non-CCC formation group (Group B, n=18). Density gradient centrifugation was applied to separate the mononuclear cells (MNCs) from coronary artery blood samples, and MNCs were cultured and proliferated in vitro. The morphology of DCs was observed under converted microscope. The number of harvested cells and DCs was counted by hematocytometer. Flow cytometry was applied to investigate the phenotype and the mean fluorescence intensity (MFI). Mixed lymphocyte reaction was used to test the function of DCs to stimulate the proliferation of T lymphocytes. Stimulation index (SI) was calculated and compared., Results: (1) After in vitro proliferation, DCs were cultured successfully from the mononuclear cells from coronary artery blood samples and the morphology of DCs was not different in the 2 groups. (2) The number of mononuclear cells (MNC no) was (3.95+/-1.41)*10(6), in the CCC group and (2.76+/-0.92)*10(6) in the non-CCC group. The MNC number was significantly increased in the CCC group (P=0.003). (3) The number of DCs was (1.54+/-0.96)*10(6) in the CCC group, and (0.99+/-0.46)*10(6) in the non-CCC group (P=0.033). (4)There was no statistical significance in the percent of CD1a+, CD1a+CD80+, CD1a+CD83+, CD1a+CD86+ cells, and MFI in the 2 groups (P>0.05). (5) SI was 4.96+/-2.30 in the CCC group, whereas 2.66+/-1.04 in the non-CCC group. The SI in the CCC group increased significantly(P=0.0003)., Conclusion: In CHD patients with severe coronary stenosis, patients with CCC formation have higher number of DCs and stronger potential of T lymphocyte stimulation.

Background: Traditional risk factors cannot account for the majority of future major adverse coronary events (MACE) in patients diagnosed with heart disease. We examined levels of inflammatory proteins to be possible predictors of future MACE and physiological and psychological factors that initiate temporal increases in inflammatory protein levels., Methods: Peripheral blood samples and depression data were collected 4 to 12 hr after elective coronary stent insertion in 490 patients. Depression screening was assessed by a single-question screening tool. Predictive modeling for future MACE was performed by using survival analysis, with time from the index event (placement of the stent) to future MACE as the dependent variable., Results: Patients with high-sensitivity c-reactive protein (hsCRP) in the second and third quartiles were 3 and 2.5 times more likely to have a MACE than patients with hsCRP in the first quartile, respectively. As levels of vascular cell adhesion molecule and monocyte chemoattractant protein-1 increased, so did the risk of future MACE. Patients who screened positive for depression were approximately 2 times more likely to have a MACE within 24 months after stent placement than were patients who did not screen positive., Conclusions: Our results suggest that hsCRP, vascular cell adhesion molecule, and monocyte chemoattractant protein-1 levels, measured after coronary stent insertion in patients with coronary heart disease, are prognostic of future MACE. Furthermore, positive depression screening is an independent predictor of future MACE.

Objective: In coronary artery disease (CAD), concomitant peripheral arterial disease (PAD) entails increased systemic inflammatory profile and more severe coronary atherosclerosis. We investigated the relationship between the inflammatory status in the affected limb and CAD severity., Methods: In 46 CAD+PAD and 31 CAD-alone patients, the inflammatory status of the leg circulation was measured by the transfemoral gradients of neutrophil myeloperoxidase (MPOx) content and interleukin-6 (IL-6). CAD severity was defined by evaluating coronary artery endothelial function, number of significant coronary stenoses, and prevalence of three-vessel CAD and myocardial infarction (MI)., Results: In the affected limb of CAD+PAD patients, the transfemoral gradients of neutrophil MPOx content and IL-6 were higher (P < .01, for both) than in the healthy leg of CAD-only patients. At multivariate analysis, CAD+PAD patients with transfemoral gradients of MPOx and IL-6 > median had a more compromised coronary artery endothelial function (P < .05, for both). Furthermore, CAD+PAD patients with transfemoral gradients of neutrophil MPOx content > median showed an independent association with a greater number of significant coronary stenoses, and a greater prevalence of three-vessel CAD and previous MI (P < .01, for all). A more severe coronary atherosclerosis was observed also in CAD+PAD patients with transfemoral gradients of IL-6 > median vs those with IL-6 < median, although differences were not statistically significant., Conclusion: In CAD patients, the coexistence of PAD does not necessarily entail a more severe coronary atherosclerosis. Only those with an inflammatory status of the affected limb presents more severe CAD. Future studies will clarify whether the presence of peripheral inflammation plays a mechanistic role in CAD evolution.

Objectives: Our aim was to determine whether serial contrast-enhanced cardiac magnetic resonance (CE-CMR) is useful for the characterization of tissue signal changes within the coronary vessel wall in patients after acute myocardial infarction (AMI)., Background: Inflammation plays a key role in the development of AMI. CE-CMR of the vessel wall has been found useful for the characterization of inflammatory tissue signal changes in patients with carotid artery stenosis, giant cell arteritis, or Takayasu's arteritis; however, it has never been serially performed in the coronary artery wall in patients with acute and chronic myocardial infarction using a gadolinium-based contrast medium and compared with systemic markers of inflammation., Methods: CE-CMR using a T1-weighted 3-dimensional gradient echo inversion recovery sequence of the coronary artery wall and 0.2 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid was performed in 10 patients with AMI 6 days and 3 months after coronary intervention and in 9 subjects without coronary artery disease on invasive coronary angiography. Contrast-to-noise ratio (CNR) within the coronary artery wall was quantified in comparison with blood signal., Results: Patients with AMI demonstrated a significantly increased coronary vessel wall enhancement 6 days after infarction compared with normal subjects (CNR 7.8 +/- 4.4 vs. 5.3 +/- 3.2, p < 0.001). Three months after infarction, CNR decreased to 6.5 +/- 4.7 (p < 0.03). This decrease paralleled declines in C-reactive protein. Angiographically normal segments showed no contrast changes, but CNR significantly decreased in stenotic segments, from 10.9 +/- 3.8 to 6.8 +/- 5.0 (p < 0.002), resulting in a reduction of enhanced segments from 70% to 25% (p < 0.01)., Conclusions: Serial CE-CMR identified changes in spatial extent and intensity of coronary contrast enhancement in patients after AMI. This technique may be useful for the characterization of transient coronary tissue signal changes, which may represent edema or inflammation during the post-infarction phase. In addition, CE-CMR may offer the potential for visualization of inflammatory activity in atherosclerosis associated with acute coronary syndromes.

Background: Outcomes in recipients who have undergone combined heart and kidney transplantation have mainly been addressed in small, single-center studies. We studied long-term results of combined heart and kidney transplantation in a large multicenter cohort., Methods: Between 1984 and 2007, 67 consecutive patients (61 men and 6 women) from 3 French centers underwent combined heart and kidney transplantation. At transplantation, 38 (57%) were receiving dialysis. All patients received immediate triple immunosuppression therapy (anti-calcineurin, steroids, azathioprine, or mycophenolate)., Results: Overall actuarial survival rates were 62.0%, 60.3%, 53.3%, and 46.5% at 1, 3, 5, and 10 years, respectively. These rates were similar to those observed in 2981 isolated heart recipients at the 3 participating centers during the same period (respectively, 71.0%, 65.2%, 60.1%, and 47.2%, p = 0.6). Survival tended to improve during the last decade (1996 to 2007) and reached 71.1%, 67.5%, and 60% at 1, 3, and 5 years. Cardiac allograft rejection requiring treatment occurred in 12 (17.9%). Coronary artery vasculopathy developed in 3 (9.3%). Kidney allograft rejection occurred in 9 (13.4%). Kidney graft survival was 95.9% at 1, 3, 5, and 10 years., Conclusions: Long-term survival rates in a large cohort of combined heart and kidney recipients are similar to those of isolated heart recipients in France. The rates of acute heart and kidney rejection and angiographic coronary artery vasculopathy were low in this patient population.

Objectives and Design: The objective of this study was to explore whether increased levels of inflammatory cytokines are associated with the risk of clinically silent coronary artery disease., Subjects: Three-hundred-fifty-six black adults aged 25-54 residing in inner city of Baltimore, Maryland, United States were included in this study., Methods: Sociodemographics were assessed as were lipid profiles, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and high-sensitivity C-reactive protein (hs-CRP) levels. Computed tomography (CT) coronary angiography was performed., Results: Coronary calcification was identified in 22.5 % participants and 14 % had significant (>or=50 %) coronary stenosis. Multiple logistic regression analyses suggested that IL-6 levels were independently associated with the presence of coronary calcification and significant coronary stenosis, while TNF-alpha, sICAM-1 and hs-CRP levels were not., Conclusions: This study underscores a critical role for IL-6 in atherosclerosis and suggests that IL-6 may be a marker for significant coronary stenosis in cardiovascularly asymptomatic individuals.

Background: In non-ST-segment elevation acute coronary syndromes (NSTE-ACS), the relation of the level of high-sensitivity C-reactive protein (CRP) to the progression of atherosclerosis remains unclear., Methods and Results: The study group comprised 153 patients with NSTE-ACS who underwent percutaneous coronary interventions (PCI) and follow-up (mean interval, 7 months) coronary angiography. Rapid progression was defined as > or =10% diameter reduction of a preexisting stenosis > or =50%, > or =30% diameter reduction of a stenosis <50%, development of a new stenosis > or =30% in a previously normal segment, or progression of any stenosis to total occlusion. Progressors had higher CRP levels on admission and at 48 h after PCI, a higher level of low-density lipoprotein cholesterol at follow-up, a higher rate of multiple complex lesions, and a lower frequency of statin use at follow-up than nonprogressors. Multivariate analysis showed that admission CRP elevation (CRP level on admission > or =0.166 mg/dl, median value; odds ratio (OR) 2.92, p=0.010), post-PCI CRP elevation (CRP level 48 h after PCI > or =1.586 mg/dl, median value; OR 2.67, p=0.022), and multiple complex lesions (OR 2.66, p=0.017) were independent predictors of rapid progression of nonculprit lesions., Conclusions: Enhanced inflammatory response to PCI, as well as baseline inflammatory activity as reflected by CRP level, may be involved in the progression of atherosclerosis in NSTE-ACS.

Background: Although some previous studies have reported that genetic and immunological factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiological factors of this enigmatical pediatric disease are still poorly understood., Purpose: This study aims to investigate whether polymorphisms of the CD40 ligand (CD40L) gene are associated with KD and the development of coronary artery lesions (CAL) in the Taiwanese children., Materials and Methods: The CD40L -3459 A/G and IVS4+121 A/G single nucleotide polymorphisms (SNPs) were genotyped in 167 children with KD and 1,010 ethnically matched healthy controls by TaqMan assay., Results: None of the CD40L polymorphisms was associated with susceptibility or CAL development of KD, and this finding was supported by the haplotype analysis., Conclusion: In summary, these results provide little support for specific CD40L SNPs in the susceptibility or CAL development of KD in Taiwanese children. However, it will be necessary to validate or replicate this association in other independent large-size ethnic groups.

Objective: To prospectively evaluate the outcome with circulating endothelial progenitor cell (EPC) capture stent implantation in a cohort of consecutive patients with high-risk angiographic and/or clinical features., Background: Genous R-stent is a stainless steel coronary stent covered with antibodies specific to EPC's surface antigens, designed to promote the formation of a confluent functional endothelial layer over the device; conceivably, this may prevent both stent thrombosis and restenosis., Methods: From November 2005 to March 2007, 80 patients received 93 EPC capture stents at Campus Bio-Medico, University of Rome. Patients had two or more of the following high-risk features: diabetes mellitus (33%), unstable coronary syndromes (73%), left ventricular dysfunction (8%), multivessel intervention (9%), B2/C lesions (56%)., Results: Acute success was achieved in 79/80 patients (98%), without Q-wave myocardial infarction (MI), in-hospital death or emergency bypass surgery; no patient had acute or subacute stent thrombosis. Follow-up was available in 78 patients (mean 14 +/- 4 months): noncardiac death occurred in one patient, acute MI in one patient; no patient required bypass surgery; 10 patients (13%) underwent percutaneous target lesion revascularization (TLR); three patients (4%) had reintervention on a nontarget vessel. Kaplan-Meyer life-table analysis showed event-free survival of 86% and TLR-free survival of 90% at one and a half year follow-up., Conclusions: The cell capture stent is safe and effective, with satisfactory immediate results and mid-term outcome, without evidence of stent thrombosis. Whether those devices represent a viable alternative to currently available drug-eluting or bare metal stents will need to be evaluated in larger randomized studies., (Copyright 2008 Wiley-Liss, Inc.)

Background: The role of Chlamydophila pneumoniae (CP) in the progression of atherosclerosis is controversial. Also no sufficient angiographic study is available about the impact of CP infection on severity and intensity of coronary atherosclerosis. We investigated the relation between CP IgG antibody titers and severity and intensity of coronary atherosclerosis, Methods: The study population consisted of 516 consecutive patients who underwent a coronary angiography. The group included 353 patients who had coronary artery disease; a control group included 163 subjects with angiographically proven normal coronary arteries. Chlamydophila pneumoniae IgG antibody titers were measured by an enzyme immunoassay method in all patients. Gensini scores and extent scores were used to evaluate the angiographic extent and severity of atherosclerosis., Results: The mean value of IgG antibody titer was 44.3 +/- 28.8 IU/mL in the patients and 39.8 +/- 27.4 IU/mL in the control group (p = 0.14). There was no statistically significant correlation between the Gensini scores, extent scores and CP IgG titers (Gensini score: r = +0.103, p = 0.07, extent score: r = +0.110, p = 0.31). When we grouped the patients as high (> 50 IU/mL) and low (< 50 IU/mL) IgG antibody titers, the number of diseased coronary arteries was higher in patients with high IgG antibody titers (respectively: 2.6 +/- 1.1 vs. 2.2 +/- 0.8, p = 0.01). While the Gensini score was significantly higher in patients with high IgG antibody titers (7.5 +/- 4.0 vs. 6.17 +/- 4.0, p = 0.01), the extent score did not change with IgG titers (29.8 +/- 15.9 vs. 25.8 +/- 15.4, p = 0.08)., Conclusions: In our study, we investigated the relation between CP infection and coronary atherosclerosis and found that CP IgG antibody titers are associated with the severity of coronary stenosis at higher antibody levels. However, there is no association between CP antibody titers and clinical presentation of coronary artery disease. We suggest that CP has limited effect on coronary atherosclerosis.

Background: Acute rejection increases the inflammatory burden of the transplanted organ and predisposes to cardiac allograft vasculopathy (CAV). In this study we aim to determine the magnitude of the association, and to differentiate between the effects of mild vs severe rejection episodes., Methods: Between 1988 and 2003, 489 1-year survivors of heart transplantation underwent 1,435 angiograms. These patients were classified as having no CAV (0% stenosis), mild/moderate CAV (<70%) or severe CAV (>70%). Acute rejection was considered either mild (Grades 1A, 1B and 2 untreated) or moderate/severe (Grade 2 treated on a clinical basis and Grades 3A, 3B and 4). We used multi-state Markov models to examine risk factors for the onset of CAV., Results: Expressed as relative risk, the onset of CAV was significantly increased by donor age (1.26 per 10 years, 95% confidence interval [CI] 1.12 to 1.42), male recipient (1.72, 95% CI 1.01 to 2.94), pre-transplant recipient ischemic disease (1.53, 95% CI 1.14 to 2.06) and cumulative number of moderate/severe rejections (1.10 per episode, 95% CI 1.03 to 1.18). Human leukocyte antigen (HLA) and cytomegalovirus (CMV) matching, donor gender, recipient age, smoking, cumulative CMV infections and mild rejections were not significant risk factors. Estimated annual onset rate of CAV was 11.3% for patients with no moderate/severe rejection, rising to 13.6% for those with two and 18.0% for those with five such rejections., Conclusions: Acute moderate/severe cellular rejection has a cumulative impact on CAV onset, whereas mild, untreated rejection is not associated with CAV.

Objective: To investigate whether Chlamydia pneumoniae (Cpn) seropositivity in patients with suspected coronary artery disease (CAD) (n = 81) is associated with increases in markers of inflammation, the severity of coronary atherosclerosis, and traditional risk factors for cardiovascular events., Material and Methods: The severity of coronary atherosclerosis was ranked by Gensini score. Inflammation and endothelial dysfunction were evaluated using white blood cell counts and levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, tumour necrosis factor-alpha (TNF-alpha), interleukins 1beta and 6 (IL-1beta, IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin and oxidized LDL (oxLDL), and these were compared between Cpn-seropositive and seronegative individuals., Results: IgA and IgG Cpn seropositivity were significantly associated with the presence of CAD (p = 0.005) and were independent predictive factors for the severity of coronary atherosclerosis (p = 0.005). Elevated levels of IL-6 (p = 0.027) and triglyceride (p = 0.038) and low levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.038) were significantly predicted by Cpn IgA and IgG seropositivity., Conclusions: Seropositivity for Cpn is a risk factor for patients with significant angiographically documented coronary stenosis. Additionally, Cpn seropositivity was significantly associated with dyslipidemia and elevated IL-6, known risk factors for CAD. These observations indicate that Cpn infection may be one entry point to the causal or contributory pathways that lead to atherosclerosis and its clinical manifestations.