Prognostic Impacts Of Plasma Levels Of Cyclophilin A In Patients With Heart Failure

Background: Cyclophilin A (CyPA) is secreted from cardiac fibroblasts in response to angiotensin II and/or mechanical stretch and promotes cardiac hypertrophy and fibrosis. However, the prognostic impact of CyPA in patients with heart failure (HF) remains to be examined. Methods and Results: In 143 consecutive patients who were hospitalized in Tohoku University Hospital for HF, we measured plasma levels of CyPA and BNP and examined their prognostic impacts during the follow-up (median 3.7 years). Plasma CyPA levels were significantly elevated in HF patients (15.3 ± 9.6 ng/mL, n = 123) than in healthy controls (5.2 ± 4.5 ng/mL, n = 20) (P < .001). Kaplan-Meier curve showed that higher CyPA levels (≥15 ng/mL) were associated with primary endpoint (all-cause death and HF rehospitalization) (HR3.6, 95%CI:1.8–8.9, P < .05) and all-cause death (HR3.7, 95%CI:1.3–10.5, P < .05). Higher BNP levels (≥100 pg/mL) were also associated with primary endpoint (HR4.6, 95%CI:1.9–11.2, P < .001) and all-cause death (HR4.3, 95%CI:1.2–15.3, P < .05). Interestingly, there was no correlation between CyPA and BNP levels, suggesting different clinical implications of the 2 biomarkers. Importantly, the combination of CyPA (≥15 ng/mL) and BNP (≥100 pg/mL) was highly significantly associated with primary endpoint (HR25.5, 95%CI:3.4–191.6, P < .01) and all-cause death (HR12.5, 95%CI:1.6–97.6, P < .05). Conclusions: These results indicate that plasma CyPA levels have prognostic impacts in HF patients, which are further enhanced when combined with BNP.