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Patients with acute coronary syndrome (ACS) associated to high C-reactive protein (CRP) levels exhibit a higher risk of future acute ischemic events. Yet, the positive predictive value of CRP is too low to guide a specific treatment. Our study aims to identify a high-risk patient subset who might mostly benefit from anti-inflammatory treatment on the basis of the combination of optical coherence tomography (OCT) assessment of the culprit vessel and CRP serum levels. Patients admitted for ACS and undergoing pre-interventional OCT assessment of the culprit vessel were selected from "Agostino Gemelli" Hospital OCT Registry. The primary end-point was recurrent ACS (re-ACS). CRP levels ≥2 mg/L were considered abnormal. The overall study population consisted of 178 patients. Among these, 156 patients were included in the primary end-point analysis. The re-ACS rate was 23% at 3-year follow-up. High CRP (2.587, 95% CI:1.345–10.325, p = 0.031), plaque rupture (3.985, 95% CI:1.698–8.754, p = 0.009), macrophage infiltration (3.145, 95% CI:1.458–9.587, p = 0.012) and multifocal atherosclerosis (2.734, 95% CI:1.748–11.875, p = 0.042) were independent predictors of re-ACS. All patients (14/14) with high CRP and with all OCT high-risk features had re-ACS. At the other extreme, only 4 of the 82 patients with low CRP levels and lack of high-risk features at OCT examination exhibited re-ACS at follow-up. The combination of systemic evidence of inflammation and OCT findings in the culprit plaque identifies very high-risk ACS. Future studies are warranted to confirm these findings and to test an anti-inflammatory treatment in this patient subset. • High CRP and OCT features of the culprit vessel predict recurrent coronary events. • Patients with high-risk OCT features and high CRP experienced a recurrent ACS. • Our findings may contribute to individualize the secondary prevention of ACS. [ABSTRACT FROM AUTHOR]

Objectives: To compare angiographic and optical coherence tomography (OCT) data pertinent to thrombi, along with the histologic characteristics of aspirated thrombi in patients presenting with ST elevation myocardial infarction (STEMI) with or without inflammation, as assessed by C-reactive protein (CRP) and myeloperoxidase (MPO). Methods: In the OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) study, 140 patients with STEMI referred for primary percutaneous intervention were enrolled. The patients underwent OCT assessment of the culprit vessel, along with blood sampling of CRP and MPO, and histologic analysis of the thrombus. Results: Biomarkers were available for 129 patients, and histology and immunohistochemistry of the thrombi were available for 78 patients. Comparisons were made using the median thresholds of CRP and MPO (2.08 mg/L and 604.124 ng/mL, respectively). There was no correlation between CRP and MPO levels in the whole population (p = 0.685). Patients with high CRP levels had higher thrombus grades and more frequent TIMI flow 0/1 compared with those with low CRP levels (5 [1st quartile 3; 3rd quartile 5] vs. 3.5 mg/L [1; 5], p = 0.007, and 69.3 vs. 48.5%, p = 0.04, respectively). Patients with high MPO levels more commonly had early thrombi than had those with low MPO levels (42.5 vs. 20.0%, p = 0.04). Conclusions: CRP and MPO were not correlated in STEMI patients, possibly reflecting different pathogenic mechanisms, with CRP more related to thrombus burden and MPO to thrombus age. [ABSTRACT FROM AUTHOR]

Aim : To assess eosinophil cationic protein (ECP) and C-reactive protein (CRP) serum levels at three time points according to different stent types. Methods : 54 patients (age 64 ± 10 years, male 78%), undergoing Bare Metal Stent (BMS) ( n = 11), mammalian Target Of Rapamycin (mTOR)-inhibitor DES ( n = 27) and mTOR-inhibitor bioabsorbable DES (BES) ( n = 16) implantation for stable angina (SA) or non-ST-elevation acute coronary syndromes (NSTE-ACS), were prospectively enrolled. ECP and CRP serum levels were assessed before revascularization, at 1-month and at 1-year after the procedure. Moreover, 21 patients found to have inducible ischemia or angina symptoms at 6 month-stress test underwent 1-year follow-up (FU) angiography. Results : Baseline and 1-month ECP levels were similar among the 3 groups, whilst 1-year ECP was significantly higher in m-TOR-DES [8.61 (6.55–19.77) μg/ml] compared with m-TOR-BES [2.03 (1.78–5.53) μg/ml] and BMS-treated patients [2.23 (1.45–8.95) μg/ml] ( p = 0.02), without significant difference between BES and BMS. CRP was similar among the 3 groups at all time points. 1-year ECP significantly correlated with late loss in patients undergoing FU angiography ( r = 0.64, p = 0.002), while CRP did not ( p = NS). Conclusions : Our finding suggests that mTOR-DES stent type is associated with an increase of ECP levels at 1-year, possibly reflecting a persistent eosinophil activation triggered by permanent polymer. [ABSTRACT FROM AUTHOR]

Our study aimed to elucidate mechanisms underlying discordance between fractional flow reserve (FFR) and hyperemic stenosis resistance (hSR) in some patient subsets. To do this, we enrolled 30 consecutive patients with stable angina or noneST elevation myocardial infarction (non-STEMI) and with a nonculprit intermediate coronary lesion (40% to 70%) by coronary angiography. We measured aortic pressure, flow velocity, and pressure distal to lesion simultaneously at basal level and during adenosine-induced (fixed intracoronary dose of 120 mg) hyperemia using a dual-sensoreequipped guidewire. Microvascular resistance (MR; pressure distal to lesion/flow velocity, mm Hg/cm/s) and variation (Δ) in MR levels were calculated both at baseline and after hyperemia, whereas FFR (cutoff <0.80) and hSR [(aortic pressure L pressure distal to lesion)/flow velocity, cutoff >0.80 mm Hg/cm/s] were assessed after intracoronary adenosine. Twenty-three patients (76.7%) showed concordance and 7 patients (23.3%) showed discordance between FFR and hSR (all cases with FFR >0.80 and hSR >0.80). Discordant patients presented more frequently with non-STEMI (85.7% vs 39.1%, p [ 0.04), significantly higher C-reactive protein serum levels (median [interquartile range] 5.9 [5.1 to 6.8] vs 4.9 [3.7 to 6.2] mg/L, p[0.007), and lower ΔMR (p[ 0.03) values compared with concordant patients. In conclusion, patients with non-STEMI and those with increased C-reactive protein levels show a lower reduction in MR after intracoronary adenosineeinduced hyperemia, leading to FFR underestimation. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). Methods and results: Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogaty''s score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64±10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30μg/L (13.8–46.9), p <0.001] and NSTE-ACS [21.8μg/L (5.5–46.3), p =0.016] compared to NCA [9.7μg/L (6.1–13.6)], without significant difference between SA and NSTE-ACS (p =0.45). CRP levels were significantly higher in NSTE-ACS [2.38mg/L (1.11–11.94)] compared to SA [1.48mg/L (0.82–2.83), p =0.03], and NCA [1.09mg/L (0.8–2.1), p <0.001], without significant difference between SA and NCA (p =0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p =0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p =0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p =0.001), whereas CRP levels independently predicted lesion complexity (p =0.01). Conclusions: Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution. [Copyright &y& Elsevier]

Abstract: Background: Previous studies have shown conflicting results about the relationship between baseline C-reactive protein (CRP) and restenosis after stenting with bare metal stent (BMS). Methods: We assessed the association between serum CRP and angiographic restenosis after BMS by meta-analysis. Studies that reported basal serum CRP levels, above a prespecified cutoff value, before BMS deployment were included. An inverse random weighted meta-analysis was performed by entering the logarithm of the odds ratio (OR) of angiographic restenosis with its standard error for each study. Results: Nine studies enrolling 2747 patients were selected. CRP threshold value was around 3 mg/l in three studies, 5 mg/l in four studies, and 6.98 and 10 mg/l in one study. Follow-up duration was 6.2±3.0 (mean±S.D.) months. Higher preprocedural CRP levels were a significant predictor of angiographic restenosis: OR 1.59, 95% confidence interval 1.21–2.07, P=.001. Heterogeneity was found: χ 2 14.47, P=.07; I 2=44.7%. Publication bias was also detected (P=.01, Egger''s test). A sensitivity analysis, after excluding each study in turn, confirmed the predictive value of higher CRP levels, in agreement with the results of the main analysis. Conclusions: Among patients with coronary artery disease, undergoing percutaneous coronary intervention with BMS, higher baseline CRP levels are associated with higher risk of angiographic restenosis. A targeted therapeutic approach to patients with high baseline CRP, based on statins, oral corticosteroids, or PPAR gamma agonists, or selective use of drug-eluting stents, aiming at abating the higher risk of in-stent restenosis should be considered. [Copyright &y& Elsevier]

Abstract: Objective: Cystatin C (Cys-C) is an accurate marker of renal function. Recent studies have shown that serum Cys-C levels predict the risk of cardiovascular events. The causes of this association, however, are largely unknown. Methods and results: Seventy consecutive patients (age 62±12, male sex 87%) undergoing coronary angiography because of typical chest pain and found to have coronary artery disease were included in the present study. Patients with abnormal creatinine-derived glomerular filtration rate (<90ml/min/1.73m2) were excluded in order to avoid the well-known effect of overt renal insufficiency on coronary atherosclerosis. Coronary angiography was evaluated by two expert angiographers who assessed disease severity and extent according to the Sullivan''s score and lesion morphology. In all patients, Cys-C and C-Reactive Protein (CRP) serum levels were measured on admission. Multivariable analysis was performed to assess independent predictors of angiographic measures. Diabetes was the only predictor of disease severity (p =0.005), while male sex (p =0.03), hypercholesterolemia (p =0.04), diabetes (p <0.0001) and Cys-C (p <0.0001) were independent predictors of disease extent. Independent predictors of smooth lesions were diabetes (p <0.001) and Cys-C (p =0.005). No correlation was found between Cys-C and CRP serum levels (p =0.6). Conclusion: Cys-C is associated with coronary atherosclerosis extent and a smooth lesion morphology. The long-term prognostic role of Cys-C might be accounted for by a greater atherosclerotic burden, a necessary substrate for plaque destabilization. [Copyright &y& Elsevier]

Abstract: Background: Previous studies have reported conflicting results on the association between C-reactive protein (CRP) and extent of atherosclerosis, suggesting that the association between CRP and outcome in patients with acute coronary syndromes is independent of coronary artery disease extent. We tested this hypothesis in a selected population of patients with unstable angina undergoing coronary angiography. Methods: Ninety-seven consecutive patients with unstable angina were enrolled in this single-centre study. All patients underwent coronary angiography. CRP was measured by an ultrasensitive nephelometric method. We also measured serum levels of soluble CD40 ligand by ELISA and plasma fibrinogen levels by use of the Clauss method. Atherosclerotic disease severity and extent were assessed by angiography using the Bogaty score. The extent index refers to the proportion of the coronary tree affected by detectable atheroma on angiography. The primary end-point at 6 months was a composite of: (a) death, (b) myocardial infarction, and (c) recurrence of unstable angina requiring hospitalization. Cardiac death was the secondary end-point. Results: No significant correlation was found between baseline CRP serum levels and angiographic measures of atherosclerotic disease severity and extent, whereas a trend for a significant correlation was found between soluble CD40 ligand and extent index (p =0.06). Diabetic patients exhibited a higher extent index compared to non-diabetic patients (0.94±0.1 versus 0.7±0.04, p =0.04). Predictors of primary end-point at both univariate and multivariate analysis were: extent index (p =0.04 and 0.04, respectively), CRP levels (p =0.05 and 0.02, respectively), and lack of revascularization (p =0.03 and 0.02, respectively). Fibrinogen levels were the only independent predictor of cardiac death at follow-up (p =0.04). Conclusion: In this study we demonstrate that in patients with unstable angina, CRP serum levels and coronary atherosclerosis are not correlated, but both are independently associated with a worse outcome at 6-month follow-up. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Background: Systemic inflammation is involved in several pathological cardiovascular processes. However, whether it plays a role in the no-reflow phenomenon occurring in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is unknown. Methods: We studies 60 consecutive patients (59.5±12 years, 82% males) with a first ST-segment elevation AMI, treated by primary or rescue PCI within 6 h of symptom onset. Angiographic indexes of no-reflow, evaluated at the end of the procedure, included coronary TIMI flow grading, corrected TIMI frame count (c-TFC) and myocardial blush grade (MBG). ECG indexes of no-reflow included the lack of ST segment resolution (defined as a reduction <50% of the measured ST-segment elevation at 90 min, compared to the admission ECG), as analyzed both in the single lead with the maximal ST elevation and in all leads showing ST elevation on admission. Patients were divided into two groups according to baseline high-sensitivity C-reactive protein (CRP) serum levels measured on admission: high CRP group (CRP>5 mg/L) and low CRP group (CRP<5 mg/L). Results: A similar prevalence of final TIMI flow<3 and MBG<3 was observed in patients with high and low CRP serum levels (30% vs. 12%, p =0.1, and 50% vs. 53%, p =1.0, respectively), and c-TFC was also similar in the two groups (26±4.5 vs. 24±6, p =0.5). Accordingly, the prevalence of lack of ST-segment resolution in the two groups was similar, both by the single-lead method (25% vs. 25%, p =1.0) and the multiple-lead method (29% vs. 19%, p =0.4). Conclusion: In this study we failed to demonstrate any significant association between CRP serum levels on admission and coronary no-reflow, as assessed by both angiographic and ECG parameters in AMI patients treated by successful primary or rescue PCI within 6 h of chest pain onset. [Copyright &y& Elsevier]

No abstract available [ABSTRACT FROM AUTHOR]

Abstract: Background: Mechanisms of instability in patients affected by unstable angina and who exhibit low levels of C-reactive protein (CRP) on admission are unclear. We compared levels of markers of thrombin generation [thrombin–antithrombin complexes (TAT), of fibrinolysis [plasmin–antiplasmin complexes (PAP)], and angiographic severity and extent of coronary atherosclerosis in patients with severe unstable angina and high or low systemic levels of CRP. Methods: Forty consecutive patients (age 59.7±8.7, 76% males) admitted to our coronary care unit with severe unstable angina (Braunwald class IIIB) were included in the present study. We assayed TAT and PAP using commercially available ELISA assays and CRP with high sensitivity nephelometry. The evaluation of atherosclerotic disease severity and extent was performed. Patients were divided in two groups according to CRP levels: G1=CRP>3 mg/L and G2=CRP<3 mg/L. Results: Number of diseased vessels and number of stenoses plus occlusion were similar between the two groups (1.8±0.9 in G1 vs 2.2±0.9 in G2, p =NS and 2.6±1.9 in G1 vs 2.7±1.3 in G2, p =NS, respectively), as well as extent score and index (8.4±4.5 in G1 vs 9.2±3.1 in G2, p =NS and 0.6±0.3 in G1 vs 0.6±0.27 in G2, p =NS, respectively). Episodic activation of thrombin generation, as assessed by TAT was more frequent in G1 than in G2 (85% vs 47%, p =0.03). Episodic activation of the fibrinolysis was more frequent in G1 than in G2 (80% vs 40%, p =0.01). Conclusion: Patients with coronary instability and systemic evidence of inflammation exhibit more frequent activation of the thrombin/fibrinolysis system than patients with a similar clinical presentation but no evidence of systemic inflammation, whereas the coronary atherosclerotic burden is similar. The mechanisms of coronary instability in the absence of systemic evidence of inflammation need to be elucidated by future studies. [Copyright &y& Elsevier]

Objective: To study the frequency of CD4+CD28null T cells, which are aggressive T lymphocytes associated with recurrent coronary instability and type 2 diabetes mellitus, in different polycystic ovary syndrome (PCOS) phenotypes and in age- and body mass index–matched healthy women. Design: Retrospective cohort observational study. Setting: Unit of human reproductive pathophysiology, university hospital. Patient(s): A total of 167 PCOS patients and 102 control subjects. Intervention(s): None. Main Outcome Measure(s): CD4+CD28null T cell frequency, high-sensitive C-reactive protein levels, and other glucose-metabolic parameters. Result(s): CD4+CD28null frequency was significantly higher in all PCOS groups than in control subjects. CD4+CD28null frequency was significantly higher in nonhyperandrogenic phenotype (5.7%, range 3.2–7.1) than in phenotypes with hyperandrogenism (H) + oligoamenorrhea (O) + polycystic ovary (PCO) (3.5%, range 1–5.8), H + O (3%, range 1.8–4.7), and H + PCO (2.63%, range 1.2–4.1). The relative risk of non-H phenotype for PCOS women in the highest quartile for CD4+CD28null frequency compared with PCOS women with the lowest quartile was 3.2 (95% confidence interval 1.9–5.8). Conclusion(s): Cardiovascular risk evaluation should be performed in all PCOS phenotypes. In particular, we demonstrated that the non-H phenotype has potentially increased cardiovascular risk in terms of CD4+CD28null frequency. [ABSTRACT FROM AUTHOR]

To compare the anti-inflammatory and endothelial progenitor cell mobilizing effects of ramipril and telmisartan in patients presenting with acute coronary syndrome (ACS), 42 patients with ACS were randomized after successful percutaneous coronary intervention to ramipril 5 mg/day (22 patients) or telmisartan 80 mg/day (20 patients). Peripheral blood samples were drawn at baseline and at 20 days to measure high-sensitivity C-reactive protein and to assess 4 populations of progenitor cells by flow cytometry, namely CD34+/KDR+, CD34+/CD133+, CD34+/CD133+/CD45−, and CD34+/KDR+/CD45− cells. High-sensitivity C-reactive protein levels, similar in the 2 groups at baseline, were significantly more decreased by telmisartan than by ramipril at follow up (p = 0.013 for time-by-drug interaction). The main effect for time was also significant (p <0.001). CD34+/KDR+ and CD34+/CD133+ cells were similar at baseline and did not change over time (p = 0.2 and p = 0.1, respectively). In contrast, for CD34+/KDR+/CD45− and CD34+/CD133+/CD45− cells, a significant increase with time was seen (p = 0.02 and p = 0.002, respectively) and no differential effect of either drug was seen. In conclusion, telmisartan shows a more potent anti-inflammatory effect than ramipril after an ACS. The 2 drugs do not show a differential effect on endothelial progenitor cell mobilization. [Copyright &y& Elsevier]

Abstract: We assessed heart rate variability (HRV) and high-sensitivity C-reactive protein (CRP) serum levels in 77 patients with chronic stable angina (CSA), 47 of whom had obstructive coronary artery disease (CAD) and 30 normal or near-normal coronary arteries (NCA). The effect of percutaneous coronary interventions (PCI) and bypass surgery (CABG) on HRV and CRP was assessed in 36 patients (18 PCI, 18 CABG) 6 months after the intervention. A significant inverse correlation was found between CRP levels and HRV variables in CAD patients (best r value=−0.31, p =0.036 for very low frequency amplitude), but not in NCA patients. At follow-up, however, no significant correlation was found between CRP and HRV in PCI and CABG treated patients. Thus, while confirming the presence of a relation between cardiac autonomic dysfunction and inflammation in CAD patients, our data show that the association is lost after revascularization procedures. [Copyright &y& Elsevier]