TY - JOUR
T1 - Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure
AU - Ebner, Nicole
AU - Földes, Gabor
AU - Schomburg, Lutz
AU - Renko, Kostja
AU - Springer, Jochen
AU - Jankowska, Ewa A.
AU - Sharma, Rakesh
AU - Genth-Zotz, Sabine
AU - Doehner, Wolfram
AU - Anker, Stefan D.
AU - von Haehling, Stephan
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Background: The origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity. Methods: LPS responsiveness was studied in 122 patients with chronic HF (mean. ±. SD: age 67.3. ±. 10.3. years, 24 female, New York Heart Association class [NYHA] class: 2.5. ±. 0.8, left ventricular ejection fraction [LVEF]: 33.5. ±. 12.5%) and 27 control subjects of similar age (63.7. ±. 7.7. years, p. >. 0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-α (TNFα) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNFα secretion). The optimal cut-off value was calculated by receiver-operator characteristic curve (ROC) analysis. Results: A total of 56 patients with chronic HF died from any cause during follow-up. At 24. months, cumulative mortality was 16.4% (95% confidence interval 16.0-16.7%). The delta TNFα value representing the optimal cut-off for the prediction of mortality was 1522. pg/mL (24. months) with a sensitivity of 49.3% (95% confidence interval 37.2-61.4%) and specificity of 81.5% (95% confidence interval 61.9-93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01-0.67, p.
AB - Background: The origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity. Methods: LPS responsiveness was studied in 122 patients with chronic HF (mean. ±. SD: age 67.3. ±. 10.3. years, 24 female, New York Heart Association class [NYHA] class: 2.5. ±. 0.8, left ventricular ejection fraction [LVEF]: 33.5. ±. 12.5%) and 27 control subjects of similar age (63.7. ±. 7.7. years, p. >. 0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-α (TNFα) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNFα secretion). The optimal cut-off value was calculated by receiver-operator characteristic curve (ROC) analysis. Results: A total of 56 patients with chronic HF died from any cause during follow-up. At 24. months, cumulative mortality was 16.4% (95% confidence interval 16.0-16.7%). The delta TNFα value representing the optimal cut-off for the prediction of mortality was 1522. pg/mL (24. months) with a sensitivity of 49.3% (95% confidence interval 37.2-61.4%) and specificity of 81.5% (95% confidence interval 61.9-93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01-0.67, p.
KW - Chronic heart failure
KW - Immune system
KW - Selenium
KW - Tumor necrosis factor-alpha
UR - http://www.scopus.com/inward/record.url?scp=84939477163&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939477163&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2015.07.029
DO - 10.1016/j.yjmcc.2015.07.029
M3 - Article
C2 - 26264758
AN - SCOPUS:84939477163
VL - 87
SP - 48
EP - 53
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
ER -