Abstract 1548: High Plasma Levels of Stromal Cell-Derived Factir-1 alpha Predict Future Cardiovascular Events in Patients with Previous Myocardial Infarction

Abstract

Stromal cell-derived factor-1 alpha (SDF-1α) is expressed in ischemic myocardium and atheromatous plaques and plays a key role in the repair of injured myocardium. We examined whether SDF-1α in circulating plasma may play a role in pathophysiology of myocardial infarction (MI). Methods and Results: SDF-1α levels in plasma from a peripheral vein (PV) were measured using ELISA in 206 consecutive patients with previous MI and in 50 age- and sex-matched controls. The levels were also measured in plasma from the aorta (AO) and the anterior interventricular vein (AIV) in a subgroup of 82 patients with anterior MI. After baseline measurements, all patients with previous MI were prospectively followed for ≤ 60 months or until occurrence of a clinical cardiovascular event: cardiac death, nonfatal myocardial infarction, refractory angina pectoris requiring coronary revascularization, or hospitalization with congestive heart failure. PV levels of SDF-1α were higher in patients with MI than controls (2750 ± 79 vs. 2351 ± 72 pg/mL, p < 0.01). In addition, PV levels were significantly higher in MI patients with (n = 42) than without an event (n = 164) (2909 ± 108 vs. 2645 ± 41 pg/mL, p < 0.01). In multivariate Cox hazard analysis, a higher level of SDF-1α (> 3040 pg/mL, defined by ROC analysis) was a predictor of the events independently of traditional coronary risk factors (hazard ratio 2.2, 95% CI 1.1 – 4.1, p < 0.01). Moreover, there was a significant step-up in SDF-1α levels in the AIV compared with the AO in patients with anterior MI (2868 ± 49 vs. 2681 ± 60 pg/mL, p < 0.05). The AIV - AO difference in SDF-1α levels, reflecting release from ischemic myocardium, correlated positively with PV levels of SDF-1α (r = 0.23, p < 0.05). Both the AIV - AO difference in SDF-1α levels and the PV levels had a significant correlation positively with PV levels of brain natriuretic peptide and inversely with left ventricular (LV) ejection fraction. Conclusions: Higher SDF-1α levels in the peripheral circulation independently predict cardiovascular events in patients with prior MI. SDF-1α is released from ischemic myocardium in proportion to the severity of LV dysfunction via a compensatory mechanism, which may partly contribute to increased circulating levels of SDF-1α in MI survivors.