Myotrophin is a more powerful predictor of major adverse cardiac events following acute coronary syndrome than N-terminal pro-B-type natriuretic peptide

Abstract

Myotrophin is a 12 kDa protein initially isolated from hypertrophied hearts of spontaneously hypertensive rats and acts by modulating NF-κB (nuclear factor κB) activity. We have reported previously the presence of myotrophin in patients with human systolic heart failure; however, its role as a predictor of MACE (major adverse cardiac events) in patients with ACS (acute coronary syndrome) is unclear. In the present study, we sought to investigate this and compared myotrophin with NTproBNP (N-terminal pro-B-type natriuretic peptide), a marker of MACE. We studied 356 patients with ACS {276 men; mean age, 63.0±12.8 years; 80.6% STEMI [ST segment elevation MI (myocardial infarction)]; and 19.4% NSTEMI (non-STEMI)}. Blood measurement was made at 25–48 h after the onset of chest pain. The plasma concentration of myotrophin and NTproBNP was determined using in-house non-competitive immunoassays. Patients were followed-up for the combined end point of death, MI or need for urgent revascularization. Over the median follow-up period of 355 (range 0–645) days, there were 28 deaths, 27 non-fatal MIs and 73 patients required urgent revascularization. Myotrophin was raised in patients with MACE compared with survivors [510.7 (116.0–7445.6) fmol/ml compared with 371.5 (51.8–6990.4) fmol/ml respectively; P=0.001; values are medians (range)]. Using a Cox proportional hazards model, myotrophin {HR (hazard ratio), 1.64 [95% CI (confidence interval), 0.97–2.76]; P=0.05} and Killip class above 1 [HR, 1.52 (95% CI, 0.93–2.42); P=0.10] were the only independent predictors of MACE. A Kaplan–Meier survival curve revealed a significantly better clinical outcome in patients with myotrophin below the median compared with those with myotrophin above the median (log rank, 7.63; P=0.006). In conclusion, after an ACS, levels of myotrophin are more informative at predicting MACE than NTproBNP and may be useful to risk stratify patients.