Plasma pentraxin 3 is a more potent predictor of endothelial dysfunction than high-sensitive C-reactive protein.

An inflammatory response is a key event for endothelial dysfunction. Pentraxin 3 (PTX3) is an inflammatory protein produced at inflammation sites such as leukocytes and vascular endothelial cells. Here, we compared the relationships between endothelial function assessed by flow-mediated dilation (FMD), and the levels of plasma PTX3 and high-sensitive C-reactive protein (hsCRP), another inflammatory protein of the pentraxin family. Levels of FMD, PTX3 and hsCRP were measured twice within 6 to 8 months and retrospectively analyzed in 36 patients with coronary artery disease. We examined the associations between the values of FMD and the levels of PTX3 and hsCRP at the first measurement, and between the change ratios (second value/first value) of these parameters. Univariate linear regression analysis showed significantly negative correlations between FMD values and PTX3 and hsCRP levels at the first measurement, and significant associations with taking statins or calcium antagonists. Multivariate linear stepwise regression analysis identified PTX3 levels and taking statins and calcium antagonists as independent factors for endothelial function. The change ratio of FMD correlated more closely with that of PTX3 than of hsCRP (r = -0.446, P = 0.006 versus r = -0.330, P = 0.050). Significantly more patients with decreased FMD values had increased levels of PTX3 than those of hsCRP at the second measurement compared with the fi rst measurement. Furthermore, the ratio of patients with increased PTX3, but not increased hsCRP, was significantly reduced among those with increased, rather than decreased, FMD values. Endothelial dysfunction might be more accurately predicted by plasma PTX3 levels than by serum hsCRP levels.

Elevated levels of systemic pentraxin 3 are associated with thin-cap fibroatheroma in coronary culprit lesions: assessment by optical coherence tomography and intravascular ultrasound.

OBJECTIVES: This study sought to determine whether systemic levels of pentraxin 3 (PTX3), a novel inflammatory marker, are associated with thin-cap fibroatheroma (TCFA). BACKGROUND: Biomarkers predicting the presence of TCFA in vivo have not been established. METHODS: We evaluated 75 patients (stable angina pectoris, n = 47; acute coronary syndrome, n = 28) with de novo culprit lesions who were examined by optical coherence tomography and intravascular ultrasound. We defined TCFA as lipid-rich plaque with a fibrous cap <65 µm thick. Systemic levels of PTX3 were compared between patients with and without TCFA. RESULTS: Thirty-eight and 37 patients with and without TCFA, respectively, were identified. Levels of PTX3 were significantly higher in patients with than in those without TCFA (p < 0.001) and correlated inversely with fibrous cap thickness (r = -0.71, p = 0.001) and positively with the remodeling index (r = 0.25, p = 0.037). Multivariate logistic regression analysis showed that a higher PTX3 level was the most powerful predictor of TCFA (odds ratio: 3.26, 95% confidence interval: 1.75 to 6.05, p < 0.001). Receiver-operating characteristic curve analysis showed that >3.24 ng/ml of PTX3 could predict TCFA with 84% sensitivity and 86% specificity. CONCLUSIONS: Higher levels of systemic PTX3 are associated with TCFA. Systemic PTX3 levels comprise a useful inflammatory marker that reflects coronary plaque vulnerability.

Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials.

AIMS: Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. METHODS AND RESULTS: Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1-Q3) = 5.34 (3.55-7.64) ng/mL, n = 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95% confidence interval (CI) 1.12-1.30, P < 0.0001], cardiovascular mortality (587 events, HR 1.27, 95% CI 1.17-1.38, P < 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95% CI 1.12-1.30, P < 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. CONCLUSION: In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. TRIAL REGISTRATION: NCT00336336 (GISSI-HF), NCT00206310 (CORONA).

Cardiac rehabilitation decreases plasma pentraxin 3 in patients with cardiovascular diseases.

BACKGROUND: Inflammatory markers such as serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma pentraxin 3 (PTX3), which belong to the pentraxin superfamily, increase due to various inflammatory diseases. Some studies demonstrated that serum CRP and SAA are predictors of cardiovascular diseases, and cardiac rehabilitation (CR) induces anti-inflammatory effects. In the present study, we investigated the effects of CR on pentraxins (serum CRP, SAA, and plasma PTX3) in patients with cardiovascular diseases. METHODS: Fifty patients with cardiovascular diseases [61 ± 13 (mean ± SD) years old, male/female 44/6] participated. Each subject performed CR using aerobic bicycle exercise two or three times per week for 3-6 months. We measured resting serum high-sensitivity CRP (hsCRP), SAA, and plasma PTX3 before and 3 and 6 months after CR, and compared them with VO(2peak) determined using a standard increment cycle ergometer protocol, B-type natriuretic peptide (BNP), and other biochemical data such as HbA1c. RESULTS: There was a significant positive correlation between hsCRP and SAA (r = 0.92, p < 0.001), but no relations between these parameters and PTX3. Plasma PTX3 significantly decreased time dependently during CR (at baseline 3.2 ± 2.0 ng/ml, at 3 months 2.3 ± 0.8 ng/ml, at 6 months 2.1 ± 0.7 ng/ml; all p < 0.05). Serum hsCRP tended to decrease, but not statistically significantly. At baseline, plasma PTX3 was negatively correlated with the percentage of the predicted values of VO(2peak) and positively correlated with BNP. CR significantly increased the percentage of the predicted values of VO(2peak) and decreased BNP. CONCLUSIONS: Plasma PTX3, an inflammatory marker, which was quite different from CRP and SAA, decreased during cardiac rehabilitation with an improvement of exercise capacity in patients with cardiovascular diseases.

Heart fatty acid-binding protein offers similar diagnostic performance to high-sensitivity troponin T in emergency room patients presenting with chest pain.

BACKGROUND: The aim of the present study was to evaluate the diagnostic accuracy of high-sensitivity troponin T (hsTnT) in patients with suspected acute coronary syndrome (ACS) in comparison to heart fatty acid-binding protein (H-FABP), high-sensitivity C-reactive protein, myeloperoxidase (MPO), and pentraxin 3 (PTX3). METHODS AND RESULTS: Patients (n=432) with chest pain were recruited for the analysis. ACS was diagnosed in 298 patients (69%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver operating curve (AUC), was highest for hsTnT (AUC=0.82; 95% confidence interval [CI]: 0.78-0.87) and H-FABP (AUC=0.83; 95%CI: 0.78-0.87). Sensitivity (87.9%) and negative likelihood (LH; 0.2) for hsTnT were the highest and lowest, respectively, but H-FABP had the highest specificity (78.5%) and positive LH (3.6). Among patients who presented within 2h after the onset of chest pain, MPO had the highest AUC (0.82; 95%CI: 0.69-0.94). Combined use of H-FABP and MPO measurements yielded a sensitivity of 69.2%, specificity of 84.2%, positive LH of 4.4, and negative LH of 0.4. CONCLUSIONS: The hsTnT assay offers excellent diagnostic performance to rule out ACS, but it is prone to false-positive results. H-FABP offers similar overall diagnostic performance, while the combination of H-FABP and MPO assays may improve the diagnosis of ACS, particularly in patients with recent onset of chest pain.

Predicting atrial fibrillation recurrence with circulating inflammatory markers in patients in sinus rhythm at high risk for atrial fibrillation: data from the GISSI atrial fibrillation trial.

BACKGROUND: Inflammation may play a significant role in the pathogenesis of atrial fibrillation (AF). OBJECTIVES: To examine the roles of three systemic inflammatory markers in predicting recurrent AF. METHODS: The association between the plasma concentrations of high-sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6) and pentraxin-3 (PTX3) with echocardiographic parameters and with the time to first recurrence of AF was tested in 382 patients with a history of AF but in sinus rhythm at randomisation, enrolled in the GISSI-AF biohumoral study. RESULTS: Baseline PTX3 was related to left atrial, but not to left ventricular chamber volume. During one year of follow-up, 204 patients (53.1%) had a recurrent AF. There were no significant differences in baseline median [Q1-Q3] plasma concentrations of IL-6, hsCRP and PTX3 among patients with (2.11 [1.47-3.74] pg/ml, 3.30 [1.40-6.80] mg/l and 4.66 [3.27-6.97] ng/ml, respectively) or without recurrent AF (2.09 [1.37-2.90] pg/ml, p=0.182; 3.00 [1.10-6.20] mg/l, p=0.333; 5.09 [3.22-7.98] ng/ml, p=0.637). At 6 and 12 months follow-up, AF patients had significantly higher concentrations of IL-6 and PTX3 than those in sinus rhythm, and those with most recent episodes of AF had higher hsCRP. Baseline levels of IL-6, hsCRP or PTX3 were not significantly associated with a higher risk of recurrence of AF. CONCLUSION: In patients with a history of AF, but without significant left ventricular dysfunction or heart failure, inflammatory biomarkers may be raised but are, at best, weak predictors of the risk for first recurrence of AF.