Abstract 829: High Plasma Levels of Stromal Cell-Derived Factor-1 Alpha Predict a Worse Prognosis in Patients with Chronic Heart Failure

Abstract

Stromal cell-derived factor-1 alpha (SDF-1α) is expressed in injured myocardium and plays a key role in the repair of the injured myocardium. This study examined whether SDF-1α in the circulation may have a prognostic information in patients with heart failure (HF). SDF-1α levels in plasma from a peripheral vein (PV) were measured using ELISA in 297 patients with chronic HF defined by the Framingham criteria, who had LV functional abnormalities (102 patients in NYHA class II, 65 in NYHA III, 32 in NYHA IV), and in 50 age- and sex-matched controls. The levels were also measured in plasma from the aorta (AO) and the coronary sinus (CS) in a subgroup of 82 HF patients. Then, all patients with HF were prospectively followed for 60 months or until occurrence of cardiac death or hospitalization with worsening HF. PV levels of SDF-1α were higher in HF patients than controls (2661 ± 67 vs. 2320 ± 55 pg/mL, p < 0.01), and patients with higher NYHA class had higher SDF-1α levels (ρ = 0.41, p < 0.0001). The PV levels of SDF-1α were similar between patients with ischemic HF (n = 204) and non-ischemic HF (n = 93). During follow-up, 19 cardiac death and 69 hospitalization occurred. The PV levels of SDF-1α were higher in patients with an event than those without an event (2820 ± 78 vs. 2490 ± 38 pg/mL, p < 0.01). In a multivariate Cox hazards analysis, a higher level of SDF-1α (> 3040 pg/mL, defined by ROC analysis) was a predictor of events that was independent of age, LVEF, use of medications, and BNP levels (HR 2.1, 95% CI 1.2–4.2, p < 0.01). Moreover, the CS - AO difference in SDF-1α levels, reflecting release from the heart, was higher in patients with (n = 21) than without an event (n = 67) (80 ± 46 vs. −32 ± 33 pg/mL, p < 0.01). The CS - AO difference in SDF-1α levels was positively correlated with the PV levels (r = 0.22, p < 0.05). Both the CS - AO difference in SDF-1α levels and the PV levels had a significant positive correlation with PV levels of BNP and an inverse correlation with LVEF. Higher SDF-1α levels in the peripheral circulation independently predict a worse outcome in patients with chronic HF. SDF-1α is released from the heart in proportion to the severity of LV dysfunction via a compensatory mechanism and may partly contribute to increased circulating levels of SDF-1α in chronic HF.