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Background: The inflammatory burden index (IBI), a novel inflammation-based indicator, to is associated with the presence and prognosis of various diseases. However, few studies have focused on exploring the relationship between IBI and the coronary slow flow phenomenon (CSFP). In this study, we aimed to investigate the predictive value of IBI for CSFP in patients with chest pain and no obstructive coronary artery disease., Methods: A total of 1126 individuals with chest pain and no obstructive coronary arteries were consecutively included in this study. 71 patients developed CSFP were included in the CSFP group. A 1:2 age- and sex-matched patient with normal blood flow and angiographically proven normal coronary arteries was selected as the control group (n = 142). Plasma C-reactive protein (CRP), neutrophil, and lymphocyte counts were measured to determine the value of IBI., Results: The IBI were significantly higher in the CSFP group than in the controls (21.1 ± 6.5 vs. 14.5 ± 6.4, P < 0.001). The IBI increasedelevated with the increase of the numbers of vessels affected by CSFP. Multivariate logistic regression analysis revealed that IBI and body mass index (BMI) were independent predictors of CSFP. Receiver operating characteristic (ROC) curve analysis showed that when IBI was > 15.74, the sensitivity and specificity were 77.5% and 67.6%, respectively, and the area under the ROC curve (AUC) was 0.799 (95% CI: 0.737-0.862, P<0.001)., Conclusion: The IBI may be an independent predictor of CSFP in patients with chest pain and normal coronary arteries. The IBI could improve the predictive value of CSFP compared with the indicators alone., (© 2024. The Author(s).)

Associations between elevated C-reactive protein (CRP) levels and the angina pectoris risk have been reported for many years, but the results remain controversial. To address this issue, a meta-analysis was therefore conducted. Eligible studies were identified by searching PubMed, EMBASE, Cochrane library, and web of science up to January 2019. Altogether, 10 prospective cohort studies and 11 case-control studies were included, and they were published from 1997 to 2013 and summed up to 18,316 samples totally. The pooled mean difference of CRP levels was 4.44 (95% confidence interval 2.71 to 6.17) between angina patients and healthy controls. The combined odds ratio of CRP for major adverse cardiac events in angina patients was 1.67 (95% CI 1.23 to 2.26). In conclusion, the meta-analysis indicated that elevated CRP levels were associated with angina pectoris, especially unstable angina pectoris, and were probably a risk factor of major adverse cardiac events., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In patients with chronic angina-like chest pain, the probability of coronary artery disease (CAD) is estimated by symptoms, age, and sex according to the Genders clinical model. We investigated the incremental value of circulating biomarkers over the Genders model to predict functionally significant CAD in patients with chronic chest pain., Methods: In 527 patients (60.4 years, standard deviation, 8.9 years; 61.3% male participants) enrolled in the European Evaluation of Integrated Cardiac Imaging (EVINCI) study, clinical and biohumoral data were collected., Results: Functionally significant CAD-ie, obstructive coronary disease seen at invasive angiography causing myocardial ischemia at stress imaging or associated with reduced fractional flow reserve (FFR < 0.8), or both-was present in 15.2% of patients. High-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST) levels, and high-sensitivity C-reactive protein (hs-CRP) were the only independent predictors of disease among 31 biomarkers analyzed. The model integrating these biohumoral markers with clinical variables outperformed the Genders model by receiver operating characteristic curve (ROC) (area under the curve [AUC], 0.70 [standard error (SE), 0.03] vs 0.58 [SE, 0.03], respectively, P < 0.001) and reclassification analysis (net reclassification improvement, 0.15 [SE, 0.07]; P = 0.04). Cross-validation of the ROC analysis confirmed the discrimination ability of the new model (AUC, 0.66). As many as 56% of patients who were assigned to a higher pretest probability by the Genders model were correctly reassigned to a low probability class (< 15%) by the new integrated model., Conclusions: The Genders model has a low accuracy for predicting functionally significant CAD. A new model integrating HDL cholesterol, AST, and hs-CRP levels with common clinical variables has a higher predictive accuracy for functionally significant CAD and allows the reclassification of patients from an intermediate/high to a low pretest likelihood of CAD., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess whether epicardial and microvascular coronary artery spasm in response to acetylcholine (ACH) is associated with markers of inflammation, platelet stimulation, and endothelial activation in patients with angina and unobstructed coronary arteries., Background: Patients with angina pectoris despite angiographically normal coronary arteries represent a diagnostic and therapeutic challenge. Both impaired coronary microvascular dilatory responses as well as diffuse distal epicardial and microvascular coronary artery spasm have been described as possible pathogenic mechanisms. Although inflammation has been proposed to play a pathogenic role in angina, an association between ACH-induced coronary vasospasm and inflammation in Caucasians has not been reported previously in this context., Patients and Methods: We assessed 62 consecutive patients (26 men, age 60±10 years) with chest pain despite angiographically unobstructed coronary arteries (<50% stenosis) who underwent intracoronary ACH testing for the diagnosis of coronary artery spasm. High-sensitivity C-reactive protein (hs-CRP), e-selectin, neopterin, and sCD40L concentrations were measured in all patients before ACH testing. The ACH test was considered to be 'positive' in the presence of (a) angina and at least 75% coronary diameter reduction (epicardial coronary artery spasm) or (b) ischemic ST-shifts and angina in the absence of epicardial spasm (microvascular spasm). Eight patients without angina pectoris served as a control group., Results: The ACH test was positive in 48 patients (77%). Twenty-seven patients had epicardial spasm (56%) and 21 patients had microvascular spasm (44%). Epicardial spasm was diffuse in 26 patients (96%) and focal in one patient (4%). Elevated hs-CRP, e-selectin, and sCD40 ligand concentrations were significantly (P≤0.05) associated with a positive ACH-test response. Hs-CRP (odds ratio 1.54, confidence interval 1.02-2.33, P=0.04) and sCD40 ligand (odds ratio 1.001, confidence interval 1.00-1.001, P=0.003) were predictors for a positive ACH test on multivariate analysis. None of the patients in the control group developed epicardial or microvascular spasm during ACH testing., Conclusion: Epicardial and microvascular coronary spasm in response to ACH correlate significantly with hs-CRP and sCD40 ligand concentrations in patients with angina pectoris and angiographically unobstructed coronary arteries. These results suggest that an association exists between inflammation and coronary artery spasm in patients with angina pectoris despite unobstructed coronary arteries and studies are needed to explore the mechanisms underlying this association.

In recent years, the scientific publications about disorder the scientific publications appeared concerning derangement of content of alpha-defensins in neutrophils of patients with atherosclerosis. The interest increases both to different derangement of protein-synthesizing function of neutrophils and to biological effects caused by defensins and other peptides and proteins taking part in anti-microbial defense of human organism. With purpose to study content of alpha-defensins (1-3) and synthesis and liberation of other proteins and peptides by neutrophils the concentrations of alpha-defensins, lipoprotein (alpha), C-reactive protein, precursor of cerebral natriuretic peptide, coagulation factor VII and von Willebrand factor were determined in supernatants of leukocytal cultures in patients with exertional angina pectoris and atherosclerosis of lower extremities. The evaluation of loading test was implemented in vitro with alpha-tumor necrosis factor in vitro. Simultaneously, serum concentrations of cytokines and pro-atherogenic proteins were analyzed. It is established that in patients with ischemic heart disease derangement of protein-synthesizing function of neutrophils is observed. The derangement is manifested in the form of decrease of synthesis of alpha-defensins, increase of synthesis of lipoprotein (alpha), precursor of cerebral natriuretic peptide, C-reactive protein and von Willebrand factor. The pathogenic role of alpha-tumor necrosis factor is established. The increase of concentration of interleukin-8 in blood serum is revealed.

Background: High levels of Pentraxin 3 (PTX3) are reported in acute myocardial infarction (AMI)., Aim: To investigate circulating levels and gene expression of PTX3 in patients with AMI and stable angina pectoris (AP) undergoing PCI., Methods: Ten patients with AP and 20 patients with AMI were included. Blood samples were drawn before PCI in the AP group and after 3 and 12 hours and days 1, 3, 5, 7, and 14 in both groups., Results: Circulating PTX3 levels were higher in AMI compared to AP at 3 and 12 hours (P < 0.001 and P = 0.003). Within the AMI group, reduction from 3 hours to all later time points was observed (all P ≤ 0.001). Within the AP group, increase from baseline to 3 hours (P = 0.022), followed by reductions thereafter (all P < 0.05), was observed. PTX3 mRNA increased in the AMI group from 3 hours to days 7 and 14 in a relative manner of 62% and 73%, while a relative reduction from baseline to 3 and 12 hours of 29% and 37% was seen in the AP group., Conclusion: High circulating PTX3 levels shortly after PCI in AMI indicate that AMI itself influences PTX3 levels. PTX3 mRNA might be in response to fluctuations in circulating levels.

Purpose: The long pentraxin 3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to proinflammatory stimuli. We reviewed the usefulness of systemic levels of PTX3 in critically ill patients with systemic inflammatory response syndrome (SIRS), sepsis, and bacteremia, focusing on its diagnostic and prognostic value., Methods: A PubMed search on PTX3 was conducted. The list of papers was narrowed to original studies of critically ill patients. Eleven papers on original studies of critically ill patients that report on PTX3 in SIRS, sepsis, or bacteremia were identified., Results: Systematic levels of PTX3 have little diagnostic value in critically ill patients with SIRS, sepsis, or bacteremia. Systemic levels of PTX3, however, have superior prognostic power over other commonly used biological markers in these patients. Systemic levels of PTX3 correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of PTX3 remain elevated in the acute phase and decreased on recovery. Notably, the age of the patients and underlying disease affect systemic levels of PTX3., Conclusions: The diagnostic value of PTX3 is low in patients with sepsis. Systemic levels of PTX3 have prognostic value and may add to prognostication of patients with SIRS or sepsis, complementing severity-of-disease classification systems and other biological markers.

Background: Early diagnosis of acute coronary syndrome (ACS) is frequently a challenging task., Aims: To assess the role of novel biomarkers to identify ACS., Methods: Concentrations of lipids, lipoproteins, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), paraoxonase-1 (PON1), secretory phospholipase A2 (sPLA2), and myeloperoxidase (MPO) were measured in 703 patients (mean age 65.5 ± 11.2 years; 422 men, 281 women) without diabetes mellitus assigned to coronary angiogram. The subjects were divided into three groups: ACS (n = 242), stable angina pectoris (SAP) (n = 242), and normal coronary artery (NCA) (n = 219)., Results: HDL-cholesterol (HDL-C) (P < 0.001) and apolipoproteinA-I concentrations (P < 0.0001) were lowest in subjects with ACS. LDL-C (P = 0.008) and non-HDL (P < 0.0001) were higher in the ACS group than in the SAP group. Leukocyte count (P < 0.0001), oxLDL (P < 0.05), hsCRP (P < 0.001), sPLA2 (P < 0.05), and MPO (P < 0.0001) were highest in the ACS group. In multivariate models, comprising all biomarkers, elevated level of MPO had the best discriminatory power to identify patients with ACS. Receiver-operating characteristic curve with and without MPO comparison differed significantly (P = 0.03 for both ACS versus NCA and ACS versus SAP)., Conclusion: Our study shows that ACS associates with low HDL-C and biomarkers of oxidative stress and inflammation. The addition of MPO in biomarker panels might improve diagnostic accuracy for ACS.

Coronary slow flow (CSF) has been documented in 25% of patients evaluated for angina or angina-like chest pain, despite the presence of normal epicardial coronary arteries on angiography. The risk for the development of clinical events in patients with non-obstructive coronary artery disease (NOCAD) is higher than in patients with completely normal coronary arteries. The object of this study was to evaluate changes in blood and plasma viscosity in patients with CSF or NOCAD. The study included 147 subjects (CSF, n = 42, NOCAD, n = 42 and controls, n = 63). Blood and plasma viscosity, complete blood counts, fibrinogen, and high sensitivity C-reactive protein (hs CRP) levels were measured. There was no significant difference between the groups with respect to blood and plasma viscosity (p > 0.05). Hemoglobin, hematocrit, and erythrocyte counts were significantly higher in the CSF group compared to the NOCAD group (p = 0.017, p = 0.023 and p = 0.023 respectively) and the control group (p = 0.026, p = 0.02 and p = 0.02, respectively). High sensitivity CRP levels in the NOCAD group were higher than the CSF group and the control group (p = 0.001 and p = 0.018, respectively). In conclusion, no significant difference was observed in the blood and plasma viscosity in patients with CSF or NOCAD. Increases in hemoglobin and hematocrit values without an increase in viscosity may play a role in the pathophysiology of CSF.

Objective: To improve cost-efficiency, discriminant functions in stepwise method was founded for the differential diagnosis of angina pectoris by detecting the serum level of high-sensitivity C-reactive protein (hs-CRP), macrophage migration inhibitory factor (MIF), interleukin-4 (IL-4) and interleukin-10 (IL-10) in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP)., Methods: Thirty-nine SAP patients and 47 UAP patients were enrolled into the study, while 39 healthy volunteers were enrolled into the controlled group forming the entire set of training samples. The serum levels of hs-CRP, MIF, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Data was analyzed by software to define discriminant functions in the ways of "entering" and "stepwise". Both functions were evaluated by the results of validation., Results: By the way of "enter independent together", the following discriminant functions were defined based on the data of training samples' age, hs-CRP, MIF, IL-4, IL-10: healthy control group =-129.858 + 2.869×age -2.451×hs-CRP + 1.393×MIF + 6.001×IL-4 + 4.848×IL-10; SAP group=-161.037 + 2.896×age-2.022×hs-CRP + 1.662×MIF + 6.703×IL-4 + 6.287×IL-10; UAP group=-199.087 + 2.468×age-1.440×hs-CRP + 3.404×MIF-13.875×IL-4 + 7.752×IL-10. Retrospective validation showed 4.8% of total miss-grouping, while cross-validation showed 5.6% of total miss-grouping. By the way of "stepwise", the above data was screened by software and training samples' age, MIF and IL-10 were suggested to define the following functions: healthy control group = - 125.218 + 2.659 × age + 0.599×MIF + 5.040 × IL-10; SAP group=-157.864 + 2.721×age + 1.008×MIF + 6.468×IL-10; UAP group=- 197.327 + 2.360×age + 2.932×MIF + 7.640×IL-10. Both retrospective and cross validation showed 6.4% of total miss-grouping. Both sets of discriminant functions had the same efficiency (100%) for differential diagnosis of SAP and UAP., Conclusion: The discriminant functions based on samples' age, MIF and IL-10, which were screened and suggested by stepwise method, may contribute to the differential diagnosis of atypical SAP and UAP, and therefore demonstrate better cost-efficiency.

Background: Pentraxin 3 (PTX3) is increased in circulating blood during the acute stage of acute coronary syndrome (ACS). Therefore, we compared diagnostic values of PTX3 for ACS with those of biomarkers for myocardial damage, such as troponin T (TnT) and heart-type fatty acid binding protein (H-FABP)., Methods and Results: Patients (n = 87) undergoing coronary angiography (CAG), consisting of 16 ACS and 71 non-ACS patients were enrolled. Non-ACS consists of 12 patients with normal CAG, 30 stable angina pectoris (SAP) patients controlled by medical treatment, and 29 SAP patients who required elective coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft). Age, gender, or prevalence of diabetes, hypertension, or smoking was not significantly different between ACS and non-ACS groups. Serum total, high-density lipoprotein, or low-density lipoprotein cholesterol, or triglyceride levels were not significantly different between ACS and non-ACS. PTX3 levels were not significantly correlated with lipid profiles or different between those with and without conventional risk factors. Circulating PTX3, TnT, and H-FABP levels were significantly higher in ACS than non-ACS. In receiver-operating characteristic (ROC) curves, area under the curve (AUC) values for PTX3, TnT and H-FABP were 0.920, 0.674, and 0.690, respectively. ROC curves of PTX3 (AUC: 0.901), TnT (AUC: 0.731), and H-FABP (AUC: 0.633) for ST-elevation ACS were similar to those for whole ACS. In a TnT-negative subgroup, the AUC values of PTX3 and H-FABP for ACS were 0.981 and 0.489, respectively., Conclusions: PTX3 is a sensitive and specific biomarker for the diagnosis of ACS, and shows additional diagnostic values when measured in combination with TnT., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: High sensitivity C-reactive protein (hsCRP) and neopterin are associated with atherosclerosis. We aimed to evaluate the association between hsCRP and neopterin, and myocardial ischemia during exercise stress test (EST) in patients with stable angina pectoris (SAP) and to assess the predictive value of these mediators in obstructive coronary artery disease., Methods: Forty-five patients with SAP were included in this prospective observational study. EST- positive group included 23 patients (15 males, mean age 54 ± 10 years) and EST-negative group-22 patients (14 males, mean age 52 ± 9 years). In each patient, blood samples were obtained 1 hour before and 30 minutes after EST. In EST-positive group, coronary angiography was performed to determine the presence and severity of coronary artery lesions as assessed by Gensini score. Statistical analysis was performed using Chi-square, unpaired t, Mann-Whitney U and Wilcoxon rank tests. Logistic regression analysis was used to establish the predictive value of tests., Results: Before EST, hsCRP and neopterin levels were similar between the two groups, however, hsCRP levels were higher in EST-positive group after EST (p=0.03). There was no significant difference between the two groups with respect to neopterin levels after EST (p=0.4). In EST-positive group, EST resulted in significant increases in both hsCRP and neopterin levels (from 3.8 ± 2.8 mg/L to 4.3 ± 3.1 mg/L, p=0.001; from 8.7 ± 4.0 nmol/L to 13.1 ± 10.0 nmol/L, p=0.001, respectively). In EST-negative group only neopterin levels significantly increased after EST (from 6.9 ± 1.8 nmol/L to 9.0 ± 3.9 nmol/L, p=0.001). No relation was observed between the obstructive coronary lesions and the levels of hsCRP or neopterin at any point., Conclusion: In SAP patients, independent with the existence of obstructive coronary lesion, elevated levels of hsCRP after EST might be an indicator of immune activation caused by myocardial ischemia.

Puerarin (4'-7-dihydroxy-8-beta-D-glucosylisoflavone), the most abundant isoflavone-C-glucoside extracted from the root of the plant Pueraria lobata, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we examined the ability of puerarin to modulate C-reactive protein (CRP) expression and key molecules in the nuclear factor kappa B (NF-kappaB) pathway to determine its molecular target. The protein and mRNA levels of CRP were determined in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells of patients with unstable angina pectoris. Also, we detected the I-kappaBalpha phosphorylation and the p65NF-kappaB expression in peripheral blood mononuclear cells under our experimental condition. The results indicated that puerarin inhibited the expression of the protein and mRNA levels of CRP in LPS-induced peripheral blood mononuclear cells. Subsequently, we determined that the inhibition of CRP expression was because of a dose-dependent inhibition of phosphorylation and degradation of inhibitor kappaB(I-kappaB), which resulted in a reduction of p65NF-kappaB nuclear translocation. We conclude that puerarin acts as an anti-inflammatory agent by blocking NF-kappaB signalling, and may possibly be developed as a useful agent for the chemoprevention of atherosclerosis.

Intensive lifestyle changes have been shown to regress atherosclerosis, improve cardiovascular risk profiles, and decrease angina pectoris and cardiac events. We evaluated the influence of the Multisite Cardiac Lifestyle Intervention Program, an ongoing health insurance-covered lifestyle intervention conducted at our site, on endothelial function and inflammatory markers of atherosclerosis in this pilot study. Twenty-seven participants with coronary artery disease (CAD) and/or risk factors for CAD (nonsmokers, 14 men; mean age 56 years) were enrolled in the experimental group and asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). Twenty historically (age, gender, CAD, and CAD risk factors) matched participants were enrolled in the control group with usual standard of care. At baseline endothelium-dependent brachial artery flow-mediated dilatation (FMD) was performed in the 2 groups. Serum markers of inflammation, endothelial dysfunction, and angiogenesis were performed only in the experimental group. After 12 weeks, FMD had improved in the experimental group from a baseline of 4.23 + or - 0.13 to 4.65 + or - 0.15 mm, whereas in the control group it decreased from 4.62 + or - 0.16 to 4.48 + or - 0.17 mm. Changes were significantly different in favor of the experimental group (p <0.0001). Also, significant decreases occurred in C-reactive protein (from 2.07 + or - 0.57 to 1.6 + or - 0.43 mg/L, p = 0.03) and interleukin-6 (from 2.52 + or - 0.62 to 1.23 + or - 0.3 pg/ml, p = 0.02) after 12 weeks. Significant improvement in FMD, C-reactive protein, and interleukin-6 with intensive lifestyle changes in the experimental group suggests > or = 1 potential mechanism underlying the clinical benefits seen in previous trials., (Copyright 2010 Elsevier Inc. All rights reserved.)

Unlabelled: C-reactive protein (CRP) is a marker for cardiovascular risk but may also participate in the pathogenesis of atherosclerosis and myocardial injury. We sought to investigate the relationship among CRP, left ventricular ejection fraction (LVEF) and symptoms of congestive heart failure (CHF) in patients with chronic stable angina (CSA) pectoris., Methods: We studied 841 patients (63+/-10 years, 72% men) with CSA undergoing coronary angiography. Symptoms of CHF were assessed using the New York Heart Association (NYHA) functional classification. CRP measurements were performed using a high sensitivity (hs-) immunoassay at the time of diagnostic coronary angiography., Results: Baseline serum hs-CRP levels showed a significant correlation with LVEF (r=-0.11; P=0.004), and prevalence of moderate-to-severe CHF correlated with serum hs-CRP quartiles (P(trend)<0.0001). After adjustment, age (P=0.004), female gender (P=0.03), body mass index (P<0.0001) and hs-CRP (OR 2.2 [1.3-3.6] CI 95%; P=0.002) were independent predictors of NYHA functional classes III-IV irrespective of LVEF and angiographic severity of CAD. A CRP value of 3.2mg/L had a sensitivity of 72%, a specificity of 75%, and a negative predictive value of 96% for detecting an impaired functional class., Interpretation: Hs-CRP serum concentrations showed an inverse correlation with LVEF and were an independent predictor of NYHA functional class in patients with CSA.

Background: Percutaneous coronary intervention (PCI) with bare metal stent (BMS) deployment causes plaque disruption and a rise in systemic levels of C-reactive protein (CRP), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Our aim is to study whether PCI with sirolimus-eluting stent (SES) use attenuates this response., Methods: Patients with stable angina undergoing single-vessel PCI were enrolled in a randomized, open-label fashion into a BMS group or an SES group. Blood samples were drawn pre-PCI, 24 hours post-PCI, and 30 days post-PCI. Systemic concentrations of CRP, IL-6, and MCP-1 were measured at all time points., Results: In total, 41 patients were enrolled (21 in the BMS group and 20 in the SES group). The baseline plasma concentrations of all markers were comparable between groups. At 24 hours, the mean plasma CRP concentration in the SES group was 20.21 mg/dL versus 8.95 mg/dL in the BMS group (P = 0.15). The mean plasma IL-6 concentration at 24 hours was 25.41 pg/mL in the SES group versus 17.44 pg/mL in the BMS group (P = 0.17). The mean plasma MCP-1 concentration at 24 hours was 382.38 pg/mL in the SES group versus 329.04 pg/mL in the BMS group (P = 0.2). At 30 days, plasma concentrations of all three markers decreased to similar values between groups., Conclusions: The use of SES did not inhibit the rise in systemic concentrations of CRP, IL-6, and MCP-1 at 24 hours or 30 days post-PCI, compared with BMS. Moreover, at 24 hours, there was a trend for higher systemic levels of all proinflammatory markers in the SES group compared with the BMS cohort.

Introduction: Inflammation is pivotal in atherosclerosis. Minor C-reactive protein (CRP) response reflects low-grade vascular inflammation and the high-sensitivity CRP test with levels > or = 3.0 mg/l predicts coronary vascular events and survival in angina pectoris as well as in healthy subjects. We and others recently reported autoantibodies against monomeric CRP (anti-CRP) in rheumatic conditions, e.g. systemic lupus erythematosus (SLE), and a connection between anti-CRP and cardiovascular disease in SLE has been suggested., Patients and Methods: Anti-CRP serum levels were determined with ELISA in 140 individuals; 50 healthy controls and 90 patients with angiographically verified coronary artery disease of which 40 presented with acute coronary syndrome (ACS) and 50 with stable angina pectoris (SA)., Results: Significantly lower anti-CRP levels were observed in ACS compared to SA and controls (p=0.019). ACS patients, who had not been prescribed statins before their respective cardiovascular event, had lower anti-CRP (p=0.049). BMI correlated directly to anti-CRP levels in cross section analysis (p=0.043), but there was no association between anti-CRP and smoking or cholesterol., Discussion: In ACS, it is plausible that ruptured plaques and inflamed tissue may be more prone to opsonization by monomeric CRP leading to consumption of anti-CRP. Hypothetically, surface-bound anti-CRP could thereby enhance the local inflammation in plaques.

The aim of our work was to find if MCP-1 -2518 (A/G) single nucleotide polymorphism (SNP) influences somehow the serum concentrations of high-sensitive CRP (hsCRP) both in patients suffering from ischemic heart disease (IHD), myocardial infarction (MI), angina pectoris (AP), and hypertension (HT) and in control group of healthy subjects. Totally, 263 patients with the diagnosis of IHD, out of them 89 with MI, 145 with AP, 205 with HT, and also 67 healthy subjects were included in the study. First, we estimated the serum levels of hsCRP. We found that patients with AP had significantly higher serum level of hsCRP than both control group of healthy subjects (P = .043) and IHD patients without AP (P = .026). The presence of the mutant G allele statistically significantly correlated with the higher serum levels of hsCRP in patients with IHD (P = .016), AP (P = .004), and HT (P = .013). Higher correlations were found in men (AP: P = .019; HT: P = .047). In all cases the highest levels of hsCRP were found both in patients and healthy controls with homozygous GG genotype.

Anginal symptoms are less predictive of abnormal coronary anatomy in women. The diagnostic accuracy of exercise treadmill test for obstructive coronary artery disease is less in young and middle aged women. High sensitive C-reactive protein has shown a strong and consistent relationship to the risk of incident cardiovascular events. Carotid intima media thickness is a non-invasive marker of atherosclerosis burden and also predicts prognosis in patients with coronary artery disease. We investigated whether incorporation of high sensitive C-reactive protein and carotid intima media thickness along with exercise stress results improved the predictive accuracy in perimenopausal non-diabetic women subset. Fifty perimenopausal non-diabetic patients (age 45 +/- 7 years) presenting with typical angina were subjected to treadmill test (Bruce protocol). Also carotid artery images at both sides of neck were acquired by B-mode ultrasound and carotid intima media thickness were measured. High sensitive C-reactive protein was measured. Of 50 patients, 22 had a positive exercise stress result. Coronary angiography done in all 50 patients revealed coronary artery disease in 10 patients with positive exercise stress result and in 4 patients with negative exercise stress result. Treadmill exercise stress test had a sensitivity of 71.4%, specificity of 66.7% and a negative predictive accuracy of 85.7% in this study group. High sensitive C-reactive protein in patients with documented coronary artery disease was not significantly different from those without coronary artery disease (4.8 +/- 0.9 mg/l versus 3.9 +/- 1.7 mg/l, p=NS). Also carotid intima media thickness was not significantly different between either of the groups with coronary artery disease positivity and negativity respectively (left: 1.25 +/- 0.55 versus 1.20 +/- 0.51 mm, p=NS; right:1.18 +/- 0.54 versus 1.15 +/- 0.41 mm, p=NS). High sensitive C-reactive protein and carotid intima media thickness were not helpful in further adding to the predictability of coronary artery disease in perimenopausal patients with typical angina as assessed by treadmill exercise stress test.

Objectives: The aim of this study was to compare concentrations of soluble intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in patients with coronary artery disease and healthy control and to evaluate the usefulness of the inflammatory markers as predictors of adverse prognosis in patients with acute coronary syndromes (ACS)., Design and Methods: ELISA was used to measure sICAM-1 and sVCAM-1 levels in 75 patients with ACS, 36 patients with stable angina pectoris (SAP) and 25 healthy subjects. hsCRP was measured with immunoturbidimetric assay, cardiac troponin T-with electrochemiluminescence immunoassay., Results: All soluble ICAM-1 and VCAM-1 significantly discriminated between patients with ACS and SAP (p=0.014 and 0.05, respectively) and control subjects (p<0.001 and 0.05). During the 6-month follow-up of the patients with ACS, there were 28 major cardiac events (37.3%). The odds ratio associated with the highest value of sVCAM-1 was 4.62 (95% CI 1.8-11.4, p=0.0009) without adjustment and remained significantly elevated after adjustment for cTnT (RR 3.93, 1.5-10, p=0.04) and hsCRP (RR 2.22, 0.8-5.7, p=0.05). In contrast, an elevated level of sICAM-1 was not associated with future coronary risk after adjustment for cTnT and hsCRP., Conclusions: In patients with acute coronary syndromes, VCAM-1 serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers.

Background: Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of acute coronary syndrome (ACS). It is of potential significance to explore the blood indexes predicting plaque characteristics. We investigated the relationship among soluble CD105, hypersensitive C-reactive protein (hs-CRP), and coronary plaque morphology., Methods: A clinical study from April 2004 to December 2006 was conducted in 130 patients who were divided into 3 groups: 56 patients (43.1%) in stable angina (SA) group, 52 patients (40.0%) in unstable angina (UA) group and 22 patients (16.9%) in acute myocardial infarction group. The concentrations of soluble CD105 and hs-CRP were measured in all of the patients by cardioangiography (CAG). Plasma samples of arterial blood were collected prior to the procedure. The levels of soluble CD105 and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA)., Results: Unstable and ruptured plaque was found more frequently in patients with acute myocardial infarction and UA. External elastic membrane cross-sectional area (EEM CSA), plaque area, lipid pool area and plaque burden were significantly larger in the ruptured and unstable plaque group. Positive remodeling, thinner fabric-cap, smaller minimal lumen cross-sectional area (MLA), dissection and thrombus were significantly more frequent in the ruptured and unstable plaque group. Remodeling index (RI) was positively correlated with the levels of soluble CD105 in the UA group (r = 0.628, P < 0.01) and the acute myocardial infarction group (r = 0.639, P < 0.01). The levels of soluble CD105 and hs-CRP were higher in the ruptured plaque group. Soluble CD105 > 4.3 ng/ml was used to predict ruptured plaque with a receiver operating characteristic (ROC) curve area of 0.77 (95% confidence interval (CI), 66.8% - 87.2%), a sensitivity of 72.8%, a specificity of 78.0% and an accuracy of 70.2% (P < 0.01), similarly for hs-CRP > 5.0 mg/ml with a ROC curve area of 0.70 (95% CI, 59.2% - 80.2%), a sensitivity of 70.2%, a specificity of 76.2% and an accuracy of 67.2% (P < 0.01)., Conclusions: The plaque characteristics correlate with the clinical presentation. The elevation of soluble CD105 and hs-CRP is related to the plaque instability and rupture.

High-sensitivity C-reactive protein (hsCRP) is an inflammation marker and potential predictor of cardiovascular events. However, there is no consensus on the relationship between plasma hsCRP levels and angiographically documented severe coronary lesions in patients with stable angina pectoris. In this study we aimed to assess whether plasma levels of hsCRP can indicate the severity of the coronary artery disease (CAD) in patients with stable angina. A total of 52 subjects, who had undergone coronary angiography were divided into two groups as follows: those with stable angina (group 1, at least one coronary arteries stenosis >50%, n = 26) and normal (group 2, n = 26). Severity of CAD was evaluated by using the Gensini score index. For each group, the levels of hsCRP were measured. HsCRP levels were compared in the subjects with normal coronary arteries, and in those with one-, two-, and three-vessel CAD, and no significant differences among the groups were found (analysis of variance, p>0.05). There was no significant correlation between hsCRP levels and Gensini score index (r = 0.278, p = 0.169). We conclude that there is no relationship between hsCRP levels and the presence and severity of CAD in patients with stable angina.

It remains unclear what kind of morphologic and biochemical features best predict plaque rupture in patients with angina pectoris (AP). This study aimed to investigate whether combined high-frequency vascular ultrasound imaging and measurements of serum inflammatory biomarkers can predict coronary plaque ruptures in patients with AP. The study population consisted of 20 patients with stable AP and 40 patients with unstable AP. High-frequency vascular ultrasound imaging was performed in the 2 groups to measure intima-media thickness, the plaque acoustic density of the common carotid arteries, and the flow-mediated dilation of the brachial arteries. Serum lipid profile and inflammatory biomarkers were measured in all patients. Using intravascular ultrasound, a list of coronary imaging parameters was obtained. A multivariate logistic regression model was applied to calculate the odds ratio of each parameter to predict coronary plaque ruptures detected by intravascular ultrasound. Of 139 coronary artery plaques identified by intravascular ultrasound, 48 plaques (9 in stable AP and 39 in unstable AP) developed ruptures. Among measured parameters, the values of carotid intima-media thickness, coronary external elastic membrane area, plaque area, plaque burden, plaque eccentric index and remodeling index, serum high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly higher in unstable AP than in stable AP (p <0.05 to 0.01). Of these parameters, carotid intima-media thickness, serum high-sensitivity C-reactive protein, and the coronary remodeling index were found to be significant predictors of coronary plaque rupture, with odds ratios of 9.51 (95% confidence interval 1.29 to 21.81), 3.02 (95% confidence interval 1.01 to 7.65), and 0.01 (95% confidence interval 0.00 to 0.34), respectively. In conclusion, combined high-frequency ultrasound imaging of coronary and carotid arteries and measurements of serum inflammatory markers are able to predict coronary plaque ruptures in patients with AP.

Background: Preprocedural C-reactive protein (CRP) serum levels have been shown to predict the recurrence of angina or major adverse cardiac events after percutaneous coronary intervention. Directional coronary atherectomy (DCA), by reducing residual plaque burden and restenosis, has been shown to improve clinical outcome after coronary stenting. Thus, we assessed the influence of preprocedural CRP serum levels on the recurrence of cardiac events after DCA followed by bare metal stent implantation., Methods: We enrolled 40 consecutive patients (34 males; 61+/-10 years old) with single-vessel disease who were undergoing DCA. In all patients, preprocedural CRP serum levels were measured by an ultrasensitive nephelometric method. The endpoint of the study was defined as the composite incidence of death, myocardial infarction, and recurrence of angina requiring repeat revascularization at 6-month follow-up., Results: CRP serum levels were a significant independent predictor of the composite endpoint at multiple regression analysis [odds ratio=1.69; 95% confidence interval (95% CI)=1.04-2.75; P=.033]. Patients with recurrence of cardiac events had CRP serum levels higher than those of patients not having events on follow-up [3.95 (2.2-5.7) vs. 2 (1.3-3.3); P=.05]., Conclusion: In conclusion, our study shows that baseline CRP serum levels predict cardiac events after coronary bare metal stenting despite plaque debulking with directional atherectomy.

Background: The aim of this study was to investigate the relation between low-grade inflammation and autonomic dysfunction, both of which may be risk markers for sudden cardiac death., Methods: A total of 269 subjects referred for elective coronary angiography because of clinically suspected coronary heart disease were included in the study. Of these 27% had a previous myocardial infarction and 70% had significant coronary stenoses. A 24-hour Holter-recording was obtained from all subjects, and time-domain heart rate variability indices were analyzed. C-reactive protein was measured using a high-sensitivity assay., Results: Mean SDNN was significantly higher in the lower compared to the upper hs-CRP quartile (140 +/- 34 ms vs 113 +/- 29 ms; P < 0.001). Similar results were found for SDNNindex (54 +/- 16 ms vs 46 +/- 12 ms; P = 0.002) and SDANN (125 +/- 33 ms vs 101 +/- 31 ms; P < 0.001). The association was strongest for subjects with a previous myocardial infarction, subjects with significant coronary stenoses, and males. In a linear regression analysis, hs-CRP remained an independent determinant of each of these three heart rate variability indices (all P < 0.001)., Conclusion: C-reactive protein and heart rate variability are independently associated. This may support a link between low-grade inflammation and autonomic dysfunction.

This study compared the recently introduced cheaper and more accessible wide-range C-reactive protein (wr-CRP) with the commonly used high-sensitivity C-reactive protein (hs-CRP) in patients undergoing coronary angiography. One hundred fifty-two consecutive patients who were admitted to a tertiary medical center and underwent angiography were included in the study. Arterial blood was obtained for the 2 assays at the beginning of angiography. A highly significant correlation (r = 0.983, p <0.001) was found between the 2 methods. This correlation was observed in different clinical scenarios and in different ranges of CRP. In conclusion, the real-time, online, and low-cost wr-CRP assay is a reasonable alternative to the Behring Dade hs-CRP method in the setting of stable and unstable coronary artery disease.

The heterogeneity in the degree of collateralization among patients with coronary artery disease (CAD) is poorly understood. We sought to determine whether chronic subclinical inflammation is related to coronary collateral development in patients with chronic stable angina pectoris and obstructive CAD. High-sensitivity C-reactive protein (CRP) levels were measured in 177 patients with stable angina pectoris before coronary angiography. Multivariable logistic regression revealed an inverse graded association between CRP and the presence of coronary collaterals (Rentrop grade 1 to 3). Compared with patients in the first CRP tertile, the adjusted odds ratio for the presence of coronary collaterals was 0.70 (95% confidence interval, 0.33 to 1.52; p = 0.45) for patients in the second CRP tertile and 0.33 (95% confidence interval, 0.15 to 0.75; p = 0.008) for patients in the third CRP tertile (p for trend = 0.008). In conclusion, an inverse graded association exists between CRP and the presence of coronary collaterals in patients with stable angina pectoris.

Background: Recent studies indicated that local inflammation played a pivotal role in the pathogenesis of coronary heart disease. Soluble CD40 ligand (sCD40L) and hsC- reactive protein (hsCRP) are important inflammatory mediators. However, whether they can reflect local coronary inflammation is unclear., Hypothesis: We hypothesized that transcoronary concentration gradient of sCD40L could reflect local inflammation in patients with coronary heart disease (CHD) more reliably., Methods: Forty subjects were divided into unstable angina pectoris (UAP) group (n=20), stable angina pectoris (SAP) group (n=10), and controls (n=10). Blood samples were collected from the coronary sinus (CS), aortic root (AO), and femoral vein (FV). The coronary circulation was expressed as CS-AO difference, while system circulation was expressed as FV-AO difference. sCD40L and hs-CRP were measured., Results: Complex lesions were more frequent in the UAP group than in the SAP group (85% vs. 40%, p < 0.05). CS-AO differences of sCD40L were much greater in the UAP group than in the SAP or control groups, and were greatly higher than FV-AO difference in UAP group (465.49 +/- 247.85 pg/mL vs. -14.94 +/- 83.41 pg/mL; 465.49 +/- 247.85 pg/mL vs. -7.66 +/- 78.54 pg/mL; 465.49 +/- 247.85 pg/mL vs. -7.99 +/- 141.34 pg/mL, all p < 0.001). CS-AO differences of sCD40L were higher in patients with complex lesions than with smooth lesions (657.86 +/- 384.76 pg/mL vs. 317.62 +/- 409.98 pg/mL, p < 0.01). There were no significant differences of CS-AO in hs-CRP among the three groups., Conclusions: In patients with CHD, the transcoronary concentration gradient of sCD40L is more sensitive than hsCRP, and sCD40L possibly a better marker of local inflammation and plaque instability., (Copyright (c) 2007 Wiley Periodicals, Inc.)

We examined whether an increase in high-sensitivity C-reactive protein (hs-CRP) after percutaneous coronary intervention (PCI) predicts long-term prognosis in patients with stable angina pectoris. hs-CRP is an inflammatory marker that predicts future cardiovascular events in healthy subjects and patients with unstable and stable coronary syndromes. Long-term evaluation of pre- and postprocedural inflammatory markers has not been widely reported. In particular, the effect of the magnitude of increase in hs-CRP after PCI in stable patients is unknown. We prospectively analyzed 89 stable patients treated by PCI for stable angina pectoris. Patients were recruited between August 1998 and May 1999, and the population was followed until August 2005 (mean follow-up 79.5 +/- 10.3 months). A major adverse cardiac event (MACE) was defined as the occurrence of cardiac death, myocardial infarction, or recurrent angina requiring repeat PCI or coronary artery bypass grafting. During the follow-up period, 36 patients presented with > or =1 MACE. In multivariate analysis, independent predictors of the occurrence of MACEs were previous myocardial infarction and a significant increase in hs-CRP after PCI (p = 0.004 and 0.003, respectively). A significant increase in hs-CRP after PCI was found to be more predictive of MACEs than hs-CRP before and after PCI. In conclusion, in stable coronary artery disease, inflammation is associated with long-term adverse events, but the magnitude of the inflammatory reaction after PCI appears more predictive than the baseline value.

Background: Platelet-monocyte aggregates (PMA) and C-reactive protein (CRP) are increased in unstable coronary disease. The interrelation of PMA with platelet activation, systemic inflammation, and their association with markers of myocardial injury has not been studied extensively., Hypothesis: The study was undertaken to evaluate the association of CRP, PMA, and cardiac troponin I (cTnI) in patients admitted with non-ST elevation acute coronary syndromes (NSTE-ACS)., Methods: In all, 69 consecutive patients with NSTE-ACS, 58 patients with stable angina pectoris (SAP), and 46 control patients without coronary artery disease were selected; PMA, sP-selectin, sCD40L inter leukin, (IL)-6, CRP, and cTnI concentrations were measured in these patients at the time of admission. Patients with NSTE-ACS were classified into two groups: those with troponin normal (cTnI < 0.06 ng/ml) and those with troponin elevation (cTnI > or = 0.06 ng/ml). Their risk for clinical in-hospital cardiac events (death and nonfatal myocardial infarction) was analyzed., Results: Compared with SAP and control, patients with NSTE-ACS exhibited higher levels of PMA, sP-selectin, sCD40L, IL-6, and CRP. All these parameters were found to be higher (p < 0.001 ) in patients with troponin elevation than in those with normal troponin. There was a significant relationship between PMA and CRP (r =0.628, p < 0.001) and cTnI (r = 0.557, p < 0.001) in patients with NSTE-ACS. Logistic analysis further demonstrated that the presence of elevated PMA, CRP, and cTnI levels each confers and increases risk of future cardiac events., Conclusions: Levels of PMA and CRP were significantly increased in patients with NSTE-ACS, especially in those with troponin elevation. This increase is strongly related to the risk of in-hospital cardiac events. A panel of PMA, CRP, and cTnI may provide important information additional to current laboratory data for the treatment of NSTE-ACS., (Copyright (c) 2007 Wiley Periodicals, Inc.)

Aims: C-reactive protein and fibrinogen have been extensively studied and shown to be predictive for a first cardiovascular event in healthy individuals. We evaluated the potential clinical use of C-reactive protein and fibrinogen in patients already suffering from coronary artery disease (CAD)., Methods and Results: In a substudy of the prospective AtheroGene registry, we assessed in 1806 patients with documented CAD and stable angina pectoris, the risk of cardiovascular death and non-fatal myocardial infarction (n=183) over a median follow-up of 3.5 (maximum 7.7) years according to baseline levels of C-reactive protein and fibrinogen. C-reactive protein and fibrinogen were associated with future cardiovascular events, such as an increment in one standard deviation of C-reactive protein is associated with a 1.15-fold (95% CI 1.05-1.27, P=0.002) increase, an increment of one standard deviation of fibrinogen with a 1.27-fold (95% CI 1.12-1.43, P<0.0005) increase in hazard risk in the models adjusted for age and sex. Adjustment for traditional risk factors and clinical confounders did not significantly attenuate this relationship. In a comparison of a basic model (traditional risk factors; AUC=0.68) with models additionally including either C-reactive protein (AUC=0.69) or fibrinogen (AUC=0.70), only little additional predictive information over that obtained from assessment of traditional risk factors was obtained., Conclusion: In patients with documented CAD, C-reactive protein and fibrinogen were predictive for future cardiovascular risk, but did not provide further information on top of that obtained from models including traditional risk factors. Our data emphasize the clinical importance of traditional risk factors in patients with CAD.

Background and Purpose: C-reactive protein (CRP) has emerged as an important predictor of cardiovascular disease, but there are few prospective data on its association with risk of ischemic stroke in patients at high risk., Methods: We examined the association between CRP levels and subsequent risk of incident ischemic stroke among 2979 patients with stable coronary heart disease included in a controlled clinical trial (Bezafibrate Infarction Prevention) that assessed the efficacy of bezafibrate, a fibric acid derivative, versus placebo for secondary prevention. CRP was measured by a high-sensitivity assay in plasma samples collected before randomization and again at the second follow-up year of an overall mean follow-up of 6.2 years., Results: Risk of ischemic stroke per 1000 person-years increased from 4.1% for baseline CRP in the lowest tertile (<2.3 mg/L; n=982) to 5.9% for levels at the middle tertile (2.3 to 5.4 mg/L; n=1013) and 10.5% for CRP levels at the upper tertile (>5.4 mg/L; n=984; P<0.001). With adjustment for potential confounders, baseline CRP levels in the top versus bottom tertile were associated with a 2.16-fold increased hazard (95% CI, 1.32 to 3.53) for ischemic stroke, and CRP levels measured after 2 years were associated with a hazard ratio of 2.43 (95% CI, 1.30 to 4.57). The risk of an incident ischemic stroke did not differ between the bezafibrate group compared with the placebo group regardless of baseline CRP levels., Conclusions: These findings, based on a large prospective study, demonstrate the risk prediction for incident ischemic stroke conferred by CRP levels in patients at high risk.

Background: Myocardial necrosis as assessed by cardiac troponin elevation occurs frequently after coronary stenting and is associated with adverse clinical outcome. Mechanical factors have been implicated in this complication and the role of systemic inflammation is not known., Methods: We prospectively studied 208 patients with chronic stable angina who underwent elective coronary stenting. All patients had normal troponin levels before the procedure. Blood samples for high-sensitivity C-reactive protein (CRP) were obtained before the procedure and analyzed using a high-sensitivity kit. Cardiac troponin T (cTnT) was obtained 24 hours after the procedure., Results: Postprocedural cTnT elevations were observed in 46 (22%) patients. There were 11 (16%), 14 (20%), and 21 (30%) patients with elevated postprocedural cTnT in the first, second, and third CRP tertile, respectively (P for trend = .045). In a multivariate logistic regression model, adjusting for all the significant univariate predictors and for statin therapy, CRP remained a significant independent predictor of postprocedural cTnT elevation with an odds ratio of 2.6 in patients in the third CRP tertile compared with patients in the first CRP tertile (95% CI 1.1-6.0, P = .02). Patients in the third CRP tertile also had higher cTnT elevations compared with patients in the first and second CRP tertile (P = .03)., Conclusions: Elevated baseline CRP levels are associated with higher risk of postprocedural troponin elevations in patients with stable angina undergoing uncomplicated coronary stenting. These results underscore the role of systemic inflammation in the pathogenesis of periprocedural myocardial injury.

Introduction: The association between plasma C-reactive protein (CRP) and the extent of coronary artery disease (CAD) in patients with stable angina remains controversial. Obesity is strongly associated with elevated CRP levels, potentially confounding the relationship between CRP and CAD severity., Methods and Results: We studied 830 subjects without CAD and 218 patients with CAD undergoing elective coronary angiography. Geometric means of CRP were computed in a two-way analysis of covariance model in which study participants were stratified into nine groups according to CAD status (no CAD, single-vessel disease or multivessel disease) and tertiles of BMI. There was a significant interaction between CAD and categories of BMI with regard to CRP level (P=0.002). In the lower tertile of BMI, patients with CAD had markedly higher CRP concentration compared to control subjects (1.16, 1.80 and 2.82 mg/L in subjects without CAD, patients with single-vessel disease and patients with multivessel disease, respectively; P=0.003). However, the relationship between CRP and CAD became weaker for patients in the second BMI tertile (P=0.15), whereas no significant relationship was observed for patients in the third BMI tertile (P=0.75). In patients undergoing coronary angioplasty (n=195), BMI was independently related to the magnitude of the angioplasty-induced CRP elevations (P=0.002)., Conclusion: The level of obesity is essential to the interpretation of the relationship between CRP and severity of CAD. The production of inflammatory mediators with increasing levels of obesity becomes the dominant determinant of plasma CRP levels and masks the vascular contribution due to CAD.

Objectives: Elevated plasma C-reactive protein (CRP) levels predict coronary events, but it is unclear whether CRP plays a role in thrombosis associated with these events. We investigated tissue factor (TF) induction by CRP on peripheral blood mononuclear cells (PBMC) from patients with coronary disease., Patients and Methods: PBMC from 35 patients with stable angina (SA) in study 1, 10 male patients with SA, 10 with unstable angina (UA) and 10 matched controls in study 2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in study 3 were stimulated with CRP, interferon-gamma (IFN) or lipopolysaccharide (LPS), or their combination. PBMC from additional normal donors were also stimulated with CRP in adherent and non-adherent conditions, and TF activity, antigen and mRNA expression detected., Results: CRP (5-25 microg mL(-1)) dose dependently induced more TF on PBMC from SA patients than 42 contemporary controls (P = 0.001, study 1). Compared with controls, patients with SA or UA had higher basal, and much higher CRP- or CRP/LPS-induced monocyte TF activity although serum CRP levels were similar (study 2). IFN induced monocyte TF activity in patients with angina, but not in controls. Basal or CRP-induced TF levels did not differ between controls and ID, even though ID patients had much higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P = 0.005) and ID (P = 0.007) in study 3, but not in patients with angina (P =0.84) in study 2. CRP induced more TF activity, protein and mRNA under adherent than non-adherent conditions implying that it may mainly target macrophages in lymphocyte-rich lesions., Conclusions: Our results indicate that monocytes from patients with angina are preactivated and express TF but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further increase TF levels that may contribute to the hypercoagulable state in coronary disease.

The evidence has indicated that rapid reduction of inflammatory marker, such as C-reactive protein (CRP) could be achieved by administration of a statin. However, limited information is available in evaluating the short-term time course of CRP reduction in patients with coronary artery disease by use of a statin. Forty-two patients with stable angina were randomly assigned to 20 mg/d or 40 mg/d group of pravastatin. Blood samples were drawn at days 0, 1, and 14 for measuring lipid profile, CRP levels, and hepatic enzymes in all patients. The results showed that both doses of pravastatin induced significant reductions in median CRP levels and in mean CRP levels, respectively, at day 1 (20% in the 20 mg/d group and 17.6% in the 40 mg/d group; 15% in the 20 mg/d group and 10% in the 40 mg/d group) as well as at day 14 (28.6% in the 20 mg/d group and 33.3% in the 40 mg/d group; 25% in the 20 mg/d group and 22.8% in the 40 mg/d group) compared with baseline data without a dose-dependent manner. In addition, no changes were found at day 1 regarding lipid profile; however, both doses of pravastatin induced significant reductions in total cholesterol (TC, 22% and 30%), and low-density lipoprotein (LDL) cholesterol (30% and 40%) compared with baseline at 14 days. The higher dose of pravastatin resulted in significantly greater reductions in TC and LDL cholesterol compared with the 20 mg/d dose (p = 0.05, p = 0.01, respectively). A less significant reduction was observed in triglycerides level (16% and 24%) compared with TC and LDL cholesterol. There was no significant difference in mean high-density lipoprotein (HDL) cholesterol levels compared with baseline in both groups. These data suggested that a common daily dose of pravastatin resulted in rapid reduction of CRP within 24 hours and of lipid profile within 2 weeks, and the benefit to the vascular endothelium might occur quickly by reduction of CRP levels, which may be clinically important for patients in a high-risk subgroup, such as acute coronary artery disease.

An elevated white blood cell (WBC) count and elevated C-reactive protein (CRP) have been associated with an increased risk of adverse cardiac events. The relation between these 2 parameters of heightened systemic inflammation was characterized in patients who underwent percutaneous coronary intervention (PCI). Femoral arterial blood samples from a prospective registry of 100 patients who underwent PCI were obtained immediately before the procedure. The concentrations of CRP and interleukin-6 were determined by an enzyme-linked immunosorbent assay. Patients were stratified according to tertiles of ascending WBC counts before PCI. Univariate analysis compared patients in the highest WBC count tertile with the lower tertiles for clinical, angiographic, and procedural characteristics, as well as pre-PCI cytokine concentrations. Multiple logistic regression analysis was performed to examine the association between the elevated WBC count and baseline elevations in either CRP or interleukin-6, accounting for the simultaneous effect of confounding characteristics. Approximately 75% of patients had stable or unstable angina pectoris versus a marker-positive acute coronary syndrome. Patients in the highest WBC count tertile were more likely to be smokers, have received unfractionated heparin, have a marker-positive acute coronary syndrome, and have a CRP >3.0 mg/L. Multivariate analysis showed that only elevated troponin-I before PCI was independently associated with the highest WBC count tertile (odds ratio 10.9, 95% confidence interval 3.7 to 32.4, p < 0.01). In patients with negative troponin I findings, CRP >3.0 mg/L was a powerful independent predictor of an elevated pre-PCI WBC count (odds ratio 3.78, 95% confidence interval 1.07 to 13.3, p = 0.04). In conclusion, in patients with troponin I negative coronary syndromes, a pre-PCI elevation in the WBC count reflected cytokine-mediated inflammation.

Objective: Recent studies demonstrate that the serum inflammatory markers increase in patients with atherosclerosis. We aimed to assess whether a difference exists between patients with acute coronary syndrome and patients with stable angina pectoris in respect to serum neopterin, procalcitonin (PCT) and C-reactive protein (CRP) levels., Methods and Results: A total of 52 patients (42 male, 10 female) who had atherosclerosis confirmed by angiography and were being followed up for an acute coronary syndrome were recruited and for control group, 45 patients with stable angina pectoris (SA) (35 male and 10 female) who underwent coronary angiography, were examined. Serum concentrations of neopterin, CRP and PCT in the study group (acute coronary syndrome) were compared to control group (stable angina pectoris). The mean neopterin level of the study group was 22.47 +/- 2.93 nmol/l, the mean CRP level was 30.40 +/- 8.05 mg/l and the mean PCT level was 0.40 +/- 0.04 ng/ml. In control group these levels were 12.26 +/- 0.61 nmol/l (p < 0.05), 5.26 +/- 0.64 mg/l (p < 0.001) and 0.19 +/- 0.02 ng/ml (p < 0.001), respectively., Conclusion: In the presented study our results showed that these markers can be useful for the assessment of inflammation related to atherosclerosis.

Objectives: We hypothesized that a higher degree of inflammatory response to coronary stenting, as measured by the change in C-reactive protein (CRP) levels after intervention in patients with stable or unstable angina, would be related to a higher risk of in-stent restenosis., Methods: We studied 1800 consecutive patients with stable or unstable angina treated with coronary stenting. C-reactive protein levels were serially measured before and after the intervention. The difference (Delta) between highest CRP values after intervention and CRP values before intervention was calculated. Patients were grouped into tertiles according to DeltaCRP values. The primary end point was angiographic restenosis (diameter stenosis > or = 50% at 6-month angiography). The secondary end point was clinical restenosis, defined as target vessel revascularization performed in the presence of angiographic restenosis and symptoms or signs of ischemia., Results: No relationship was found between CRP values at baseline and angiographic restenosis (P = .88). On the other hand, the change between baseline and peak postintervention CRP values strongly correlated with angiographic restenosis (30.5% in the upper tertile with DeltaCRP values >11.8 mg/L, 25.3% in the middle tertile with DeltaCRP values 3.0-11.8 mg/L, and 21.5% in the lower tertile with DeltaCRP values < 3.0 mg/L, P = .002) as well as with clinical restenosis (P = .01). Patients in the upper tertile had the highest risk of restenosis even after adjustment for other covariates., Conclusions: The inflammatory response to coronary stenting as assessed by the change in CRP correlates with the development of in-stent restenosis. These findings provide strong support for the role of inflammation in restenosis.

Objectives: To evaluate the relationship between serum C-reactive protein (CRP) levels and disease activities of vasospastic angina pectoris., Methods: We reviewed 284 consecutive patients who underwent the coronary artery vasospasm provocation test with intracoronary administration of acetylcholine. No patient had significant organic stenosis in the coronary artery on control angiography. No patient was given nitrates, calcium channel blockers, aspirin or statins before the provocation test. Serum CRP levels were measured on the day before the provocation test., Results: Significant transient coronary artery stenoses associated with chest symptoms and ST-T changes in electrocardiogram was found in 132 patients (positive group), but the remaining 152 showed no spasm (negative group). Serum CRP levels were significantly higher in the positive group than in the negative group (0.29 +/- 0.12 vs 0.08 +/- 0.06mg/dl, p < 0.01). Furthermore, high frequency of angina pectoris ( > or = 3 times/week), low dose of acetylcholine required to induce vasospasm, provocation of total occlusion and provocation of multivessel spasm were associated with significantly higher serum CRP levels in the positive group. Multivariate logistic regression analysis showed low dose of acetylcholine required to induce vasospasm as the strongest predictor of elevated levels of serum CRP (p < 0.001, odds ratio 4.52, 95% confidence interval 2.00-10.44)., Conclusions: Serum CRP levels were related to the inductivity of coronary artery spasm in patients clinically suspected of having vasospastic angina pectoris. Inflammation may be important in the disease activity through the endothelial dysfunction of coronary artery trees.

Objectives: The purpose of this study was to assess local release of C-reactive protein (CRP) from atherosclerotic plaques or the vessel wall injured by stenting., Background: Recent research has focused on the local production of CRP, especially in inflammatory atherosclerotic plaques., Methods: The study consisted of two separate protocols. In protocol 1, we measured serum high-sensitivity-CRP (hs-CRP) levels in coronary arterial blood sampled just distal and proximal to the culprit lesions in 36 patients with stable angina and 13 patients with unstable angina. In protocol 2, we measured serial serum hs-CRP levels and activated Mac-1 on the surface of neutrophils in both coronary sinus and peripheral blood in 20 patients undergoing coronary stenting., Results: In protocol 1, CRP was higher in distal blood than proximal blood in both stable (p < 0.05) and unstable angina (p < 0.01). The translesional CRP gradient (distal CRP minus proximal CRP, p < 0.05) as well as the proximal CRP (p < 0.05) and distal CRP (p < 0.05) was higher in unstable angina than in stable angina. In protocol 2, the transcardiac CRP gradient (coronary sinus minus peripheral blood) and activated Mac-1 increased gradually after stenting, reaching a maximum at 48 h (p < 0.001 vs. baseline for both). There was a positive correlation between the transcardiac CRP gradient and activated Mac-1 at 48 h (r = 0.45, p < 0.01)., Conclusions: C-reactive protein is an excellent marker for plaque instability or poststent inflammatory status, and its source might be the inflammation site of the plaque or the coronary arterial wall injured by stenting.

To assess the value of serial C-reactive protein (CRP), serum amyloid A (SAA), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) evaluation in the risk stratification in patients undergoing percutaneous coronary intervention. The study was designed as a prospective cohort trial with a 1-year follow-up. Eighty patients (70 with stable angina, 10 with unstable angina) were enrolled. Blood samples were collected before the procedure and after 6 and 24 h, and 1 month. Clinical follow-up visits were performed (*with exercise test) 7 days* and 1*, 3, 6* and 12 months after the procedure. Any symptoms of restenosis were verified angiographically. Multivariate logistic regression analysis identified increased preprocedural TNF-alpha and CRP levels and elevated CRP concentrations evaluated 24 h after the procedure as significant predictors of both clinical restenosis and major adverse cardiac events (MACE), while high SAA values at 24 h accurately predicted clinical restenosis. Patients, who were in the highest tertile of, either, baseline TNF-alpha and/or baseline CRP/CRP at 24 h, were more prone to develop restenosis and MACE than stratified only on the basis of a single marker. Our data indicate that combined analysis of CRP and TNF-alpha might be an effective approach to the clinical restenosis and MACE prediction. Additionally, long-term outcome is markedly influenced by the periprocedural activation of inflammation.

Inflammation plays an important pathogenic role in the initiation and progression of atherosclerotic plaque lesions. C-reactive protein (CRP), which directly participates in plaque inflammation, induces vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells. However, the levels and values of high-sensitivity (hs)-CRP, white blood cell (WBC) count, and VCAM-1 in both stable and unstable angina pectoris (AP) have not been fully investigated. This study examines the levels and values of these inflammatory markers in patients with stable or unstable AP. From March 2003 to December 2003, a prospective cohort study was conducted in 128 consecutive patients, including unstable AP patients (class I: n = 59; combined class II and III: n = 16) and stable AP patients (n = 53) undergoing elective coronary stenting. Blood samples for hs-CRP, WBC count, and VCAM-1 were obtained in the catheterization laboratory before coronary angiography. The circulating levels of hs-CRP and VCAM-1 were also evaluated in 40 healthy volunteers. The circulating levels of these three inflammatory markers were substantially higher in patients than in healthy volunteers (all P values < 0.0001). Additionally, circulating levels of hs-CRP and the WBC count were significantly higher in patients with unstable AP than in patients with stable AP (all P value < 0.0001). However, only those patients with class II and III unstable AP had significantly higher circulating levels of VCAM-1 than patients with stable AP (P < 0.0001). On the other hand, the circulating levels of VCAM-1 did not differ between patients with class I unstable AP and patients with stable AP (P = 0.782). Multiple stepwise logistic regression analysis showed that only hs-CRP level was independently associated with unstable AP (P = 0.0002). In conclusion, circulating levels of hs-CRP, WBC count, and VCAM-1 were significantly increased in patients with AP. The circulating level of hs-CRP was strongly associated with the clinical setting of unstable AP.

The effects of nifedipine on inflammation and endothelial function in the coronary circulation were studied in patients who had angina pectoris (n = 17). Long-term treatment with nifedipine (nifedipine CR, 20 mg/day for 4 months) decreased levels of C-reactive protein in the coronary sinus (from 0.35 +/- 0.09 mg/dl to 0.07 +/- 0.01 mg/dl, mean +/- SEM, p <0.05) and enhanced acetylcholine-induced increases in coronary blood flow. Thus, nifedipine is effective in decreasing inflammation and incresing endothelial function in the coronary circulation.

Background: The systemic inflammatory response to percutaneous coronary intervention (PCI) is associated with recurrent cardiac events; however, the pathophysiology of this inflammatory response is not well understood. The present study was performed to investigate the role of pathogen burden of infection in determining the magnitude of C-reactive protein (CRP) and interleukin 6 (IL-6) response to PCI., Methods: One hundred patients with stable angina pectoris undergoing elective PCI at a single center were recruited. Antibodies against cytomegalovirus, Chlamydia pneumoniae , Epstein-Barr virus, Helicobacter pylori , and herpes simplex virus types 1 and 2 were determined before PCI. Plasma CRP and IL-6 levels were measured before and 6, 24, 48, 72 hours after PCI and data presented as area under the curve., Results: Plasma CRP and IL-6 concentrations increased significantly after PCI. Neither antibodies against single nor multiple pathogens were associated with the CRP or IL-6 response to PCI. No correlations were found between the inflammatory markers and troponin T levels after PCI. With the exception for CRP and body mass index (R = 0.20, P < .05), neither risk factors for coronary heart disease nor medication but stent implantation was associated with increased plasma CRP (76 vs 61 mg/L, P < .005) and IL-6 (74 vs 64 pg/mL, P < .005) levels after PCI., Conclusion: Stent implantation, but not pathogen burden, is associated with the plasma CRP and IL-6 response to PCI.

Background: C-reactive protein (CRP) has been well recognized as a strong independent predictor of short-term and long-term mortality after non-ST-segment elevation acute coronary syndromes. However, limited studies have been conducted correlating CRP levels within 6 h following the onset of ST-segment elevation (ST-se) acute myocardial infarction (AMI) to mortality. The purpose of this study was to evaluate the predictive value of CRP measured by high-sensitivity CRP assay (hsCRP) on 30-day clinical outcomes in patients with ST-se AMI of onset < 6 h undergoing primary percutaneous coronary intervention (PCI)., Methods and Results: We conducted a prospective cohort study in 146 consecutive patients with ST-se AMI of onset < 6 h who were undergoing primary PCI. Blood samples for hsCRP were obtained in the catheterization laboratory before coronary angiography. Patients were classified into high (group 1: hsCRP > 2.37 mg/L, n = 73) and low (group 2: hsCRP