Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation

Alexander P Benz, Stefanie Aeschbacher, Philipp Krisai, Giorgio Moschovitis, Steffen Blum, Pascal Meyre, Manuel R Blum, Nicolas Rodondi, Marcello Di Valentino, Richard Kobza, Maria Luisa De Perna, Leo H Bonati, Jürg H Beer, Michael Kühne, Stefan Osswald, David Conen, BEAT‐AF, Swiss‐AF Investigators, Alexander P Benz, Stefanie Aeschbacher, Philipp Krisai, Giorgio Moschovitis, Steffen Blum, Pascal Meyre, Manuel R Blum, Nicolas Rodondi, Marcello Di Valentino, Richard Kobza, Maria Luisa De Perna, Leo H Bonati, Jürg H Beer, Michael Kühne, Stefan Osswald, David Conen, BEAT‐AF, Swiss‐AF Investigators

Abstract

Background Hospitalization for heart failure (HF) is very common in patients with atrial fibrillation (AF). We hypothesized that biomarkers of inflammation can identify patients with AF at increased risk of this important complication. Methods and Results Patients with established AF were prospectively enrolled. Levels of hs-CRP (high-sensitivity C-reactive protein) and interleukin-6 were measured from plasma samples obtained at baseline. We calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile). Individual associations of biomarkers and the inflammation score with HF hospitalization were obtained from multivariable Cox proportional hazards models. A total of 3784 patients with AF (median age 72 years, 24% prior HF) were followed for a median of 4.0 years. The median (interquartile range) plasma levels of hs-CRP and interleukin-6 were 1.64 (0.81-3.69) mg/L and 3.42 (2.14-5.60) pg/mL, respectively. The overall incidence of HF hospitalization was 3.04 per 100 person-years and increased from 1.34 to 7.31 per 100 person-years across inflammation score categories. After multivariable adjustment, both biomarkers were significantly associated with the risk of HF hospitalization (per increase in 1 SD, adjusted hazard ratio [HR], 1.22; 95% CI, 1.11-1.34 for log-transformed hs-CRP; adjusted HR, 1.48; 95% CI, 1.35-1.62 for log-transformed interleukin-6). Similar results were obtained for the inflammation score (highest versus lowest score, adjusted HR, 2.43; 95% CI, 1.80-3.30; P value for trend <0.001). Conclusions Biomarkers of inflammation strongly predicted HF hospitalization in a large, contemporary sample of patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Keywords: C‐reactive protein; atrial fibrillation; heart failure; hospitalization; inflammation; interleukin‐6.

Conflict of interest statement

Kobza reports institutional grants from Abbott, Biosense‐Webster, Biotronik, Boston Scientific, Medtronic, and Sis Medical. Bonati reports consultancy or advisory board fees or speaker’s honoraria from Amgen, Bayer, Bristol‐Myers Squibb, Claret Medical, and InnovHeart, and travel grants from AstraZeneca and Bayer. Beer reports institutional grants from the Swiss National Foundation of Science and The Swiss Heart Foundation. Kühne reports personal fees from Bayer, Boehringer Ingelheim, Pfizer BMS, Daiichi Sankyo, Medtronic, Biotronik, Boston Scientific, and Johnson & Johnson; and grants from Bayer, Pfizer BMS, and Boston Scientific. Conen reports speaker honoraria from Servier Canada, outside of the current work. The remaining authors have no disclosures to report.

Figures

Figure 1. Cumulative incidence of heart failure…
Figure 1. Cumulative incidence of heart failure hospitalization across inflammation score categories (Kaplan‐Meier method).

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