Endocrine Abstracts

Introduction: α-Defensins are recently described peptides, which are part of the innate immune system. Increased circulating levels are observed in conditions associated with chronic low grade inflammation, such as ischemic heart disease and in diabetes mellitus (DM). Recently we reported adverse prognostic implications of high α-defensins in patients with type 1 DM. However, it is not clear whether this finding may be generalized to include other groups such as patients with chronic heart failure (CHF). Therefore the aims were to compare plasma levels of α-defensins in CHF patients and healthy controls, and to examine the predictive ability of α-defensins with respect to all-cause mortality and future cardiovascular outcome.

Methods and design: Prospective observational study, median follow-up of 2.6 years, the prognostic value of plasma α-defensins with respect to overall mortality and new ischemic events in 194 CHF patients and 98 age-matched healthy controls.

Results: α-Defensins levels were two times higher among patients with severe heart failure (NYHA class III/IV) than in patients in NYHA class I/II and healthy controls (P=0.001). After adjustment for potential confounders including NT-proBNP, high α-defensins (>540 ng/ml) corresponding to the optimal cut-off value, were associated with a twofold increased mortality risk hazard ratio (HR) being 2.1 (95% CI: 1.2–4.1; P=0.029) and of new ischemic events HR: 1.86 (95% CI: 1.15–3.01; P=0.01). The combination of high α-defensins and high NT-proBNP levels (above the respective median values) were associated with a threefold increase in mortality HR: 3.19 (95% CI: 1.68–6.06; P<0.001), as compared to patients with low levels of both biomarkers.

Conclusion: α-Defensins are novel interesting biomarkers of chronic inflammation. In heart failure patients α-defensins provide incremental prognostic information to established clinical risk markers.