Background:
Circulating biomarkers reflecting pathways implicated in heart failure (HF) may improve HF risk assessment in patients with stable atherosclerotic cardiovascular disease (ASCVD).
Hypothesis:
We aimed to evaluate the performance of circulating biomarkers of hemodynamic stress, myocardial injury, and inflammation for the prediction of hospitalization for HF (HHF) in a large well-characterized cohort with stable ASCVD followed for a median of 4.1 years.
Methods:
HPS3/TIMI 55-REVEAL was a randomized, double-blind, placebo-controlled trial of the CETP inhibitor anacetrapib in patients with stable ASCVD. We performed a nested prospective biomarker study, measuring high-sensitivity troponin T (hsTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) (all Roche Diagnostics) at randomization (n=29,673). Hazard ratios were adjusted for covariates of
a priori
clinical relevance to HHF risk: age, prior HF, hypertension, diabetes mellitus, eGFR <60, body-mass index, and polyvascular disease. Discrimination was assessed using Harrell’s c-index.
Results:
A significant graded risk of HHF was observed with increasing deciles of hsTnT, NT-proBNP, and GDF-15 (p-trend <0.001 for each) (
Figure
). These associations remained significant after multivariable adjustment for clinical risk factors (p<0.001 for each). When added to a multivariable Cox regression model of clinical risk indicators (c-index 0.74), these 3 biomarkers significantly improved the prognostic performance of the model (c-index 0.85; p<0.001). There was no treatment interaction with anacetrapib.
Conclusions:
In patients with stable ASCVD, biomarkers of myocardial injury, hemodynamic stress, and inflammation provide incremental information for prediction of HHF. Future studies should address whether these patients are more likely to benefit from emerging HF preventive therapies.
MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure
