Cardiac Troponin I and Risk of Cardiac Events in Patients With Heart Failure and Preserved Ejection Fraction

BACKGROUND: Levels of cTn (cardiac troponin) are frequently elevated in patients with heart failure (HF) and reduced ejection fraction (EF) and correlate with the risk for mortality. However, factors associated with high cTn concentrations and the association with cardiovascular events in patients with HF and preserved EF are unclear. METHODS AND RESULTS: Of 1767 subjects with symptomatic HF with preserved EF from the Americas part of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial), 236 underwent baseline measurements of high-sensitivity (hs) cTnI using the Abbott Architect STAT assay. Baseline factors correlated with hs-cTnI levels were assessed in stepwise linear regression models and the association between hs-cTnI and adjudicated study outcomes was examined in Cox models. The median hs-cTnI concentration at baseline was 6.3 ng/L (interquartile range, 3.4-12.9 ng/L) with levels detectable in 99.2% of patients. Higher hs-cTnI concentrations were associated with male sex, black race, lower estimated glomerular filtration rate and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. After multivariable adjustment, higher concentrations of hs-cTnI were associated with greater risk for the composite of cardiovascular death or HF hospitalization (69 events during mean follow-up 2.6±1.5 years): hazard ratio 1.42 (95% CI, 1.20-1.69), P<0.001 per doubling of hs-cTnI. Compared with those in the lowest quartile of hs-cTnI, patients in the highest quartile demonstrated a nearly 5-fold higher risk of cardiovascular death and HF hospitalization (hazard ratio 4.85 1.99-11.83, P=0.001). There was no interaction between hs-cTnI and spironolactone treatment with regard to the primary composite end point (interaction P=0.94). CONCLUSIONS: In ambulatory patients with HF with preserved EF, levels of hs-cTnI are higher in male patients with black race, lower estimated glomerular filtration rate, and higher NT-proBNP. As in those with HF and reduced EF, higher hs-cTnI levels are independently associated with risk for cardiovascular death and HF hospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00094302.