Limited Incremental Benefit Offered by Cystatin C in Acute Heart Failure | Journal Scan

Study Questions:

In patients with acute decompensated heart failure (ADHF), what is the relationship between values of baseline and changes in cystatin C (CysC) between dyspnea response, short-term clinical outcomes, and nesiritide response?


This was a biomarker substudy of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial. ASCEND-HF was a multicenter, randomized, double-blind, placebo-controlled trial of nesiritide. Plasma CysC levels were measured in sequential plasma samples from 811 subjects with ADHF who were enrolled in ASCEND-HF. Co-primary endpoints were improvement in dyspnea at 6 or 24 hours, and the composite endpoint of hospital stay for HF or death at 30 days.


Although baseline CysC was a strong and independent predictor of adverse events in univariate and select multivariate analyses, this relationship did not persist after adjustment for standard measures of renal function (e.g., blood urea nitrogen). Changes in CysC were not predictive of intermediate- or long-term all-cause mortality, and changes in CysC levels were similar between the nesiritide and placebo groups (i.e., nesiritide did not have a significant favorable or deleterious impact on renal function, as assessed by CysC levels).


Although baseline levels of CysC are associated with adverse events in ADHF, this relationship does not persist after adjusting for standard measures of renal function. And, nesiritide-treated and placebo-treated groups did not differ with respect to changes in CysC levels.


CysC, a protease inhibitor that is freely filtered and neither secreted nor reabsorbed from the blood stream, has been lauded by some as an improved marker for glomerular filtration rate. The authors of this biomarker study make the valuable observation that baseline and changes in CysC levels may not offer incremental prognostic value beyond traditional renal indices. The role of monitoring CycC levels in ADHF remains uncertain.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Biological Markers, Cystatin C, Dyspnea, Heart Failure, Natriuretic Peptide, Brain, Length of Stay, Treatment Outcome, Protease Inhibitors

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