Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

Zoltán Prohászka; Lea Munthe-Fog; Thor Ueland; Timea Gombos; Arne Yndestad; Zsolt Förhécz; Mikkel-Ole Skjoedt; Zoltan Pozsonyi; Alice Gustavsen; Lívia Jánoskuti; István Karádi; Lars Gullestad; Christen P Dahl; Erik T Askevold; George Füst; Pål Aukrust; Tom E Mollnes; Peter Garred

doi:10.1371/journal.pone.0060976

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

Zoltán Prohászka, Lea Munthe-Fog, Thor Ueland, Timea Gombos, Arne Yndestad, Zsolt Förhécz, Mikkel-Ole Skjoedt, Zoltan Pozsonyi, Alice Gustavsen, Lívia Jánoskuti, István Karádi, Lars Gullestad, Christen P Dahl, Erik T Askevold, George Füst, Pål Aukrust, Tom E Mollnes, Peter Garred

Department of Clinical Medicine

21 Citations (Scopus)

Abstract

Background:Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure.Methods and Results:MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3.Conclusions:This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation.

Original language	English
Article number	e60976
Journal	P L o S One
Volume	8
Issue number	4
Pages (from-to)	1-9
Number of pages	9
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0060976
Publication status	Published - 15 Apr 2013

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Prohászka, Z., Munthe-Fog, L., Ueland, T., Gombos, T., Yndestad, A., Förhécz, Z., Skjoedt, M-O., Pozsonyi, Z., Gustavsen, A., Jánoskuti, L., Karádi, I., Gullestad, L., Dahl, C. P., Askevold, E. T., Füst, G., Aukrust, P., Mollnes, T. E., & Garred, P. (2013). Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure. P L o S One, 8(4), 1-9. [e60976]. https://doi.org/10.1371/journal.pone.0060976

Prohászka, Z, Munthe-Fog, L, Ueland, T, Gombos, T, Yndestad, A, Förhécz, Z, Skjoedt, M-O, Pozsonyi, Z, Gustavsen, A, Jánoskuti, L, Karádi, I, Gullestad, L, Dahl, CP, Askevold, ET, Füst, G, Aukrust, P, Mollnes, TE & Garred, P 2013, 'Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure', P L o S One, vol. 8, no. 4, e60976, pp. 1-9. https://doi.org/10.1371/journal.pone.0060976

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title = "Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure",

abstract = "Background:Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure.Methods and Results:MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3.Conclusions:This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation.",

author = "Zolt{\'a}n Proh{\'a}szka and Lea Munthe-Fog and Thor Ueland and Timea Gombos and Arne Yndestad and Zsolt F{\"o}rh{\'e}cz and Mikkel-Ole Skjoedt and Zoltan Pozsonyi and Alice Gustavsen and L{\'i}via J{\'a}noskuti and Istv{\'a}n Kar{\'a}di and Lars Gullestad and Dahl, {Christen P} and Askevold, {Erik T} and George F{\"u}st and P{\aa}l Aukrust and Mollnes, {Tom E} and Peter Garred",

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doi = "10.1371/journal.pone.0060976",

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T1 - Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

AU - Prohászka, Zoltán

AU - Munthe-Fog, Lea

AU - Ueland, Thor

AU - Gombos, Timea

AU - Yndestad, Arne

AU - Förhécz, Zsolt

AU - Skjoedt, Mikkel-Ole

AU - Pozsonyi, Zoltan

AU - Gustavsen, Alice

AU - Jánoskuti, Lívia

AU - Karádi, István

AU - Gullestad, Lars

AU - Dahl, Christen P

AU - Askevold, Erik T

AU - Füst, George

AU - Aukrust, Pål

AU - Mollnes, Tom E

AU - Garred, Peter

PY - 2013/4/15

Y1 - 2013/4/15

N2 - Background:Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure.Methods and Results:MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3.Conclusions:This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation.

AB - Background:Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure.Methods and Results:MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3.Conclusions:This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation.

U2 - 10.1371/journal.pone.0060976

DO - 10.1371/journal.pone.0060976

M3 - Journal article

SN - 1932-6203

VL - 8

SP - 1

EP - 9

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

M1 - e60976

ER -

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

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