title: Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  NCT00336336 (GISSI-HF), NCT00206310 (CORONA).
authors: Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, via Giuseppe La Masa 19, 20156 Milan, Italy. roberto.latini@marionegri.it
authors: Roberto
authors: R
authors: Latini
authors: Lars
authors: L
authors: Gullestad
authors: Serge
authors: S
authors: Masson
authors: Ståle Haugset
authors: SH
authors: Nymo
authors: Thor
authors: T
authors: Ueland
authors: Ivan
authors: I
authors: Cuccovillo
authors: Mari
authors: M
authors: Vårdal
authors: Barbara
authors: B
authors: Bottazzi
authors: Alberto
authors: A
authors: Mantovani
authors: Donata
authors: D
authors: Lucci
authors: Nobuhito
authors: N
authors: Masuda
authors: Yukio
authors: Y
authors: Sudo
authors: John
authors: J
authors: Wikstrand
authors: Gianni
authors: G
authors: Tognoni
authors: Pål
authors: P
authors: Aukrust
authors: Luigi
authors: L
authors: Tavazzi
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism*; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use*; D018570:Risk Assessment; D000068718:Rosuvastatin Calcium; D000683:Serum Amyloid P-Component / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000627:therapeutic use*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D000683:Serum Amyloid P-Component; D013449:Sulfonamides; D000099153:Pentraxins