Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure

Background: In patients admitted with acute heart failure (AHF), plasma levels of antigen carbohydrate 125 (CA125) have shown to be useful for risk stratification. We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF-readmission following admission for AHF.

Methods: The derivation cohort included consecutive patients admitted with AHF (n=3231). CA125 cut-off values measured during early admission that yielded a 90% negative predictive value (NPV) and sensitivity up to 85% were identified. Then, the adequacy of these cutpoints and the risk of 1-month death/HF-readmission was further tested in the multivariate survival analysis using the Royston-Parmar method. The cutpoint associated with the best-fitted model (using AIC and BIC criteria) was deemed as the optimal cutpoint. The chosen cutpoint was externally validated in a cohort of patients hospitalized from the BIOSTAT-CHF (n=1583).

Results: In the derivation cohort, median (IQR) CA125 was 57 U/mL (25.3-157); The optimal cut-off was < 23 U/ml (21.5% of patients), which yielded a NPVs of 99.3% and 94.1% for death and the composite endpoint, respectively. In multivariable survival analyses, a CA125<23 U/mL was independently associated with a lower risk of death (HR=0.20, CI 95%:0.08-0.50;p<0.001) and the combined endpoint (HR=0.63, CI95%:0.45-0.90; p=0.009). The ability of this cutpoint for discriminating patietns at low 1-month risk was confirmed in the validation cohort (NPVs of 98.6% and 96.6% for deaths and the composite endpoint). This predicted ability of this cut-off remained significant at 6-month follow-up.

Conclusions: In patients admitted with AHF, patients with CA125<23 U/mL identified a subgroup of patients at low risk of short-term adverse events, a population that may not require intense post-discharge monitoring.