Do inflammatory markers predict outcome in systolic heart failure?

The prognostic value of inflammatory cytokines in heart failure with reduced ejection fraction seems to be limited.

PhD student Ståle Haugset Nymo has looked at the relationship between increased immune activation and prognosis in patients with heart failure. Of all the inflammatory markers examined, only interleukin-8 showed an independent association with outcome, but its clinical utility as a prognostic biomarker is unclear.

The doctorate is based on data from the CORONA study, which included heart failure patients older than 60 years of age from 21 different countries. In two separate studies Nymo and colleagues show that plasma levels of the inflammatory markers NGAL, TNF-α, sTNF-RI, sTNF-RII og MCP-1 do not add prognostic value beyond known risk markers in this patient groups. Higher levels of most markers were associated with increased risk of cardiovascular death or non-fatal coronary heart disease or stroke during follow-up, even after adjustments for conventional clinical variables. However, associations were lost after further adjustments for kidney function (eGFR), ApoB/ApoA-1 ratio, general inflammation (hs-CRP) and NT-proBNP.

For interleukin-8 the association persisted in the most adjusted model. However, there was limited value of combining levels of interleukin-8 and NT-proBNP to assess the risk of adverse outcome, compared to levels of NT-proBNP alone.

A third article indicate that nucleosomes could be a potential biomarker in chronic heart failure. 30 of 179 included patients died during the three-year follow-up, and the risk was highest among patients with nucleosome levels in the upper tertile. This association was independent of other risk factors. Nucleosomes could be released to the circulation and activate the immune system following tissue damage. Given the limited sample size and small numbers of death, these results shoud be interpreted with caution.


Thesis: Inflammatory Biomarkers in Cardiovascular diseases
 Ståle Haugset Nymo
Time and place: March 17, 2017, Oslo University Hospital


Nymo, S. H., Ueland, T., Askevold, E. T., Flo, T. H., Kjekshus, J., Hulthe, J., Wikstrand, J., McMurray, J., van Veldhuisen, D. J., Gullestad, L., Aukrust, P., & Yndestad, A. (2012). The association between neutrophil gelatinase‐associated lipocalin and clinical outcome in chronic heart failure: results from CORONA. Journal of internal medicine, 271(5), 436-443.

Nymo, S. H., Hulthe, J., Ueland, T., McMurray, J., Wikstrand, J., Askevold, E. T., Yndestad, A, Gullestad, L., & Aukrust, P. (2014). Inflammatory cytokines in chronic heart failure: interleukin‐8 is associated with adverse outcome. Results from CORONA. European journal of heart failure, 16(1), 68-75.

Nymo, S. H., Ueland, T., Askevold, E., Dahl, C. P., Gullestad, L., Aukrust, P., & Yndestad, A. (2016). Circulating nucleosomes in chronic heart failure. International journal of cardiology, 203, 742-743.

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