Abstract 18454: Novel Extracellular Matrix Biomarkers as Predictors of Adverse Outcome in Chronic Heart Failure
Background: The extracellular matrix (ECM) plays an important role in left ventricular remodeling and changes in expression patterns of ECM proteins may contribute to the progression of heart failure (HF). Endostatin, biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated if they were increased in chronic HF and if levels were associated with adverse outcome.
Materials and methods: Serum endostatin, biglycan and mimecan were measured in 187 HF patients and 57 matched healthy controls. Associations with adverse outcome were assessed in 1428 patients enrolled in the in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo, which included patients with HF, aged ≥60 years, in New York Heart Association classes II to IV, who had ischemic heart disease and a reduced left ventricular ejection fraction. Outcome included the primary endpoint (cardiovascular (CV) death, nonfatal myocardial infarction, nonfatal stroke; n=408), all-cause mortality (n=422), CV mortality (n=344), coronary endpoint (n=330) and CV mortality/hospitalization for worsening of HF (n=535).
Results: Serum levels of endostatin, biglycan and mimecan were all increased (31-62% p<0.001) in HF patients vs. controls. In univariate analyses and multivariable analysis (adjusting for LVEF, NYHA class, age, BMI, diabetes, sex, intermittent claudication, heart rate, serum creatinine and apoA1 but not CRP and NT-proBNP), endostatin (continuous variable) was associated with all outcomes. However, the predictive value was markedly attenuated and not significant for any outcome after the addition of CRP and NT-proBNP. Biglycan was moderately but significantly associated with all outcome measures (except coronary endpoint) in univariate analysis but not after multivariable adjustment while no associations were observed for mimecan.
Conclusions: Serum levels of the ECM proteins endostatin, biglycan and mimecan are all elevated in chronic HF, but add no predictive information beyond NT-proBNP for adverse outcome in older patients with advanced chronic systolic HF of ischemic aetiology.
- © 2013 by American Heart Association, Inc.