Endogenous serum erythropoietin and no-reflow in patients with ST-elevation myocardial infarction

Abstract

In models of acute ischaemia, erythropoietin (EPO) administration has been found to attenuate vascular injury largely through reduced apoptosis, suppressed inflammation and increased nitric oxide availability. We studied the association between circulating endogenous EPO and no-reflow in patients with first ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Blood sampling was performed before PPCI. Consecutive patients with (n = 24) or without (n = 24) evidence of angiographic no-reflow after PPCI were enrolled. Angiographic no-reflow was defined as Thrombolysis in Myocardial Infarction (TIMI) flow ≤ 2 or as TIMI flow = 3 but with myocardial blush grade < 2. We also assessed electrocardiographic (ECG) no-reflow as ≤ 50% resolution of maximal ST elevation 60 min after PPCI. Baseline characteristics did not correlate significantly with EPO concentrations. In contrast, both angiographic and ECG no-reflow correlated with lower EPO levels at univariate analysis [median (interquartile): 4·2 (0·6-9·5) vs. 12·2 (5·2-20·3) mIU mL(-1), P = 0·001, and 4·0 (0·6-7·1) vs. 9·3 (1·0-12·6) mIU mL(-1), P = 0·01, respectively]. At multivariable analysis, decreasing EPO tertiles and left anterior descending as the infarct-related artery were the only factors that predicted both angiographic and ECG no-reflow (P = 0·017 and P = 0·02 for EPO; P < 0·005 and P > 0·05 for left anterior descending artery, respectively). We found an independent, graded, inverse relation between endogenous EPO levels and angiographic and ECG no-reflow following PPCI. In animal models of ischaemia, EPO has been found to be protective. In humans, endogenous EPO may contribute to offset the mechanisms responsible for no-reflow.