George Markousis-Mavrogenis1, Jasper Tromp2, Robert J Mentz3, Christopher M O'Connor4, Marco Metra5, Piotr Ponikowski6, John R Teerlink7, Gad Cotter8, Beth Davison8, John G F Cleland9, Michael M Givertz10, Dirk J van Veldhuisen1, Hans L Hillege11, Adriaan A Voors1, Peter van der Meer12. 1. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 2. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; National Heart Center Singapore, Hospital Drive, Singapore. 3. Duke University Medical Center, Durham, North Carolina. 4. Inova Heart and Vascular Institute, Falls Church, Virginia. 5. University of Brescia, Brescia, Italy. 6. Medical University, Clinical Military Hospital, Wroclaw, Poland. 7. University of California San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California. 8. Momentum Research, Durham, North Carolina. 9. University of Hull, Kingston upon Hull, United Kingdom. 10. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 11. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 12. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: p.van.der.meer@umcg.nl.
Abstract
BACKGROUND: Elevated plasma interleukin-6 (IL-6) concentrations are frequently observed in patients with acute heart failure (AHF). However, the predictive value of serial IL-6 measurements beyond brain natriuretic peptide (BNP) remains poorly characterized. METHODS AND RESULTS: This was a retrospective analysis of the PROTECT cohort (2033 patients with AHF). Plasma IL-6 and BNP levels were determined on days 1, 2, 7 and 14 after admission for AHF in 1591 (78.3%), 1462 (71.9%), 1445 (71.1%) and 1451 (71.4%) patients, respectively. The primary endpoint was 180-day all-cause mortality. The median day-1 IL-6 concentration was 11.1 pg/mL (IQR: 6.6, 20.9) and decreased to 10.1 pg/mL (IQR: 5.6-18.5) at day-7. Higher cross-sectional IL-6 concentrations at all time-points predicted the primary endpoint, independent of a risk model for this cohort and changes in BNP. Each doubling of IL-6 between day-1 and day-7 predicted the primary endpoint independent of baseline IL-6 concentrations, the risk model, baseline BNP and changes in BNP [HR (95% CI): 1.18 (1.07-1.30), p=0.0013]. Collectively, 214 (17%) patients experienced at least a doubling of their IL-6 concentrations between day-1 and day-7. CONCLUSIONS: We demonstrate that the temporal evolution patterns of IL-6 in patients with AHF have additive prognostic value independent of changes in BNP.
BACKGROUND: Elevated plasma interleukin-6 (IL-6) concentrations are frequently observed in patients with acute heart failure (AHF). However, the predictive value of serial IL-6 measurements beyond brain natriuretic peptide (BNP) remains poorly characterized. METHODS AND RESULTS: This was a retrospective analysis of the PROTECT cohort (2033 patients with AHF). Plasma IL-6 and BNP levels were determined on days 1, 2, 7 and 14 after admission for AHF in 1591 (78.3%), 1462 (71.9%), 1445 (71.1%) and 1451 (71.4%) patients, respectively. The primary endpoint was 180-day all-cause mortality. The median day-1 IL-6 concentration was 11.1 pg/mL (IQR: 6.6, 20.9) and decreased to 10.1 pg/mL (IQR: 5.6-18.5) at day-7. Higher cross-sectional IL-6 concentrations at all time-points predicted the primary endpoint, independent of a risk model for this cohort and changes in BNP. Each doubling of IL-6 between day-1 and day-7 predicted the primary endpoint independent of baseline IL-6 concentrations, the risk model, baseline BNP and changes in BNP [HR (95% CI): 1.18 (1.07-1.30), p=0.0013]. Collectively, 214 (17%) patients experienced at least a doubling of their IL-6 concentrations between day-1 and day-7. CONCLUSIONS: We demonstrate that the temporal evolution patterns of IL-6 in patients with AHF have additive prognostic value independent of changes in BNP.