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α-Defensins and outcome in patients with chronic heart failure
Heidi M Christensen1, Jan Frystyk, Jens Faber
1Department of Cardiology, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark. heidichristensen@dadlnet.dk
Insights
Elevated plasma alpha-defensins (α-defensins) predict mortality in chronic heart failure (CHF) patients. These innate immune molecules offer additional prognostic value beyond established markers like NT-proBNP.
Area of Science:
- Immunology
- Cardiology
- Biomarker Discovery
Background:
- Innate immunity involves alpha-defensins (α-defensins).
- Low-grade inflammation is implicated in chronic heart failure (CHF) pathogenesis.
- Established biomarkers for CHF prognosis exist, but improved prediction is needed.
Purpose of the Study:
- Compare plasma α-defensin levels in CHF patients versus healthy controls.
- Evaluate the prognostic ability of α-defensins for all-cause mortality in CHF.
- Assess the combined predictive value of α-defensins and N-terminal pro brain natriuretic peptide (NT-proBNP).
Main Methods:
- Prospective observational study of 194 CHF patients and 98 controls over 2.6 years.
- Plasma α-defensin levels measured and compared across NYHA functional classes and with controls.
- Prognostic value of α-defensins, alone and with NT-proBNP, analyzed concerning all-cause mortality.
Main Results:
- CHF patients exhibited significantly higher plasma α-defensin levels than controls.
- Higher α-defensin levels correlated with increased mortality risk (30% absolute increase in upper vs. lowest tertile).
- Plasma α-defensins independently predicted all-cause mortality in CHF, even after adjusting for NT-proBNP (HR 1.65).
Conclusions:
- Plasma α-defensins possess prognostic information for mortality in CHF patients.
- α-defensins provide incremental prognostic value beyond established clinical risk markers.
- The combination of α-defensins and NT-proBNP enhances risk prediction in heart failure.
Aim:
α-Defensins are part of the innate immune system. Low-grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of α-defensins in CHF patients and healthy controls and to examine the predictive ability of α-defensins, alone and combined with N-terminal pro brain natriuretic peptide (NT-proBNP), with respect to all-cause mortality.
Methods And Results:
In a prospective observational study lasting 2.6 years we examined the prognostic value of plasma α-defensins with respect to mortality in 194 CHF patients, and compared plasma levels with those of 98 age-matched healthy controls. α-Defensin levels were twice as high among CHF patients in New York Heart Association (NYHA) functional class III-IV than in patients in NYHA class I-II and healthy controls (P = 0.001). The absolute increase in risk of mortality for patients with α-defensin levels in the upper tertile vs. the lowest tertile was 30% (P = 0.002). After adjusting for potential confounders including NT-proBNP, plasma α-defensins remained independently associated with an increased risk of all-cause mortality (hazard ratio 1.65, 95% confidence interval 1.19-2.28, P = 0.002) per 1 standard deviation increment in Ln (natural logarithm)-transformed α-defensin values. The combination of high α-defensins and NT-proBNP levels provided incremental prognostic information independent of well-known prognostic biomarkers in heart failure.
Conclusion:
Plasma α-defensins appear to have prognostic information regarding mortality among patients with CHF and seem to provide incremental information to established clinical risk markers.
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