IL-6 and hsCRP predict cardiovascular mortality in patients with heart failure with preserved ejection fraction

Martin Berger (Aachen)1, W. März (Mannheim)2, A. Niessner (Wien)3, G. Delgado (Mannheim)4, M. Kleber (Mannheim)4, H. Scharnagl (Graz)5, N. Marx (Aachen)1, K. Schütt (Aachen)1

1Uniklinik RWTH Aachen Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin Aachen, Deutschland; 2SYNLAB Holding Deutschland GmbH SYNLAB Akademie Mannheim, Deutschland; 3Universitätsklinikum AKH Wien Medizinische - Universität Wien Innere Medizin II, Klinische Abteilung für Kardiologie Wien, Österreich; 4Universitätsklinikum Mannheim Med V. - Nephrologie, Endokrinologie und Rheumatologie Mannheim, Deutschland; 5Klinisches Institut für Medizinische und Chemische Labordiagnostik Graz, Österreich



Inflammation accompanies heart failure (HF). However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. 



To investigate the prognostic relevance of inflammatory biomarkers in patients with HFrEF and HFpEF


Methods and Results

Interleukin-6 (IL-6) and high-sensitive C-reactive Protein (hsCRP) levels were measured in 1086 patients (HFrEF N=580, HFpEF N=506) who were referred for coronary angiography between 1997 and 2000 and participated in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). During a median follow-up of 9.9 years, 240 (41%) and 133 (26%) cardiovascular (CV) deaths occurred in HFrEF and HFpEF patients, respectively. After full-adjustment, increasing IL-6 levels were associated with increased CV mortality in HFpEF (1.9 (95%CI: 1.3 – 2.8, p = 0.005) but not HFrEF (HR 1.4 (95%CI: 1.0 - 1.7), p = 0.10) patients. High-sensitive CRP followed a similar pattern but failed to reach statistical significance after full-adjustment. Interaction analysis in patients stratified by high and low levels of IL-6 and NT-pro-BNP revealed a stepwise increase in CV-mortality in HFpEF (p=0.036) but not HFrEF patients (p=0.220). To investigate the relationship between IL-6 and NT-pro-BNP, we assessed the genetic IL6-Receptor variant p.Asp358Ala (rs2228145) which is linked to impaired IL-6 receptor signaling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT-proBNP levels compared to wildtype carriers (HFpEF 779 pg/ml ± 787 versus 1180 pg/ml ± 1532; p=0.008; HFrEF 2289 pg/ml ± 3439 versus 2326 pg/ml ± 3386; p=0.94), raising the hypothesis that IL-6 signaling may play a pathophysiological role in HFpEF.



This data suggests a predictive value of elevated IL-6 for CV-mortality in HFpEF but not in HFrEF patients.

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