Cardiorenal interaction and heart failure outcomes. A role for insulin-like growth factor binding protein 2?

Abstract

Introduction and objectives: Preliminary results suggest that high circulating insulin-like growth factor binding protein 2 (IGFBP2) levels are associated with mortality risk in heart failure (HF) patients. As IGFBP2 levels are increased in patients with chronic kidney disease (CKD), which is associated with a higher mortality risk in HF patients, we examined whether IGFBP2 is associated with CKD in HF patients, and whether CKD modifies the prognostic value of this protein in HF patients.

Methods: HF patients (n=686, mean age 66.6 years, 32.7% women) were enrolled and followed up for a median of 3.5 (min-max range: 0.1-6) years. Patients were classified as having CKD with decreased estimated glomerular filtration rate (eGFR <60mL/min/1.73 m²) or as having CKD with nondecreased eGFR (≥ 60mL/min/1.73 m²). Serum IGFBP2 was detected by ELISA.

Results: IGFBP2 was increased (P <.001) in CKD patients with decreased eGFR (n=290, 42.3%) compared with patients with nondecreased eGFR. IGFBP2 was directly associated with NT-proBNP (P <.001) and inversely associated with eGFR (P <.001), with both associations being independent of confounding factors. IGFBP2 was directly and independently associated with cardiovascular and all-cause death (P <.001) in the whole group of patients, but showed a stronger association with cardiovascular death in CKD patients with decreased eGFR (P for interaction <.05), improving risk prediction in these patients over clinically relevant risk factors.

Conclusions: Serum IGFBP2 is associated with impaired renal function and prognosticates cardiovascular death in patients with HF and CKD with decreased eGFR. Thus, there is an effect modification of CKD on circulating IGFBP2 and on its association with cardiovascular mortality in HF patients.

Keywords: Cardiovascular death; Chronic kidney disease; Enfermedad renal crónica; Heart failure; IGFBP2; Insuficiencia cardiaca; Muerte cardiovascular.