title: Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.
abstract: Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, 93042 Regensburg, Germany. christoph.birner@klinik.uni-regensburg.de
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Birner
authors.forename: Coskun
authors.initials: C
authors.lastname: Ulucan
authors.forename: Sabine
authors.initials: S
authors.lastname: Fredersdorf
authors.forename: Munhie
authors.initials: M
authors.lastname: Rihm
authors.forename: Hannelore
authors.initials: H
authors.lastname: Löwel
authors.forename: Jan
authors.initials: J
authors.lastname: Stritzke
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Stephan
authors.initials: S
authors.lastname: Holmer
authors.forename: Günter
authors.initials: G
authors.lastname: Riegger
authors.forename: Andreas
authors.initials: A
authors.lastname: Luchner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009419:Nerve Tissue Proteins / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*; D012333:RNA, Messenger / Q000097:blood; D011817:Rabbits; D013045:Species Specificity; D018487:Ventricular Dysfunction, Left / Q000097:blood
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C063382:prepro-brain natriuretic peptide; D020097:Natriuretic Peptide, Brain