Abstract
BackgroundInflammatory 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 ResultsMBL, 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.ConclusionsThis 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.
Highlights
Chronic heart failure (CHF) is initiated by a variety of insults, including myocardial infarction and ischemic heart disease, hypertension, valvular abnormalities, as well as various forms of cardiomyopathies, which result in impaired myocardial function [1]
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
Summary
Chronic heart failure (CHF) is initiated by a variety of insults, including myocardial infarction and ischemic heart disease, hypertension, valvular abnormalities, as well as various forms of cardiomyopathies, which result in impaired myocardial function [1]. There is an adaptive compensatory response to preserve the overall function. These compensatory responses may in turn eventually lead into maladaptive responses with development of progressive myocardial dysfunction and overt heart failure. 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
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