Pro-Substance P for Evaluation of Risk in Acute Myocardial Infarction

Study Questions:

What is the potential role of Subtance P (SP) in acute myocardial infarction (AMI) and its association with major adverse cardiac events (MACE) such as death, heart failure (HF), or reinfarction?


Pro-substance P (ProSP) was measured in 1,148 (825 males, mean age 66.2 ± 12.8 years) AMI patients. Endpoints were MACE (composite of death, re-infarction, and heart failure [HF] hospitalization), death/reinfarction, and death/HF. GRACE (Global Registry of Acute Coronary Events) scores were compared with ProSP for death and/or reinfarction at 6 months.


During 2-year follow-up, there were 140 deaths, 112 HF hospitalizations, and 149 re-AMIs. ProSP levels were highest on the first 2 days following admission and related to estimated glomerular filtration rate, age, history of diabetes, ischemic heart disease or hypertension, Killip class, left ventricular wall motion index, and sex. Multivariate Cox regression models showed ProSP level was a predictor of MACE (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.54; p < 0.002), death and/or AMI (HR, 1.42; 95% CI, 1.20-1.68; p < 0.0005), death and/or HF (HR, 1.38; 95% CI, 1.14-1.67; p < 0.001). ProSP levels were independent predictors of 6-month death and/or reinfarction together with GRACE scores (p < 0.0005 for both). ProSP-adjusted GRACE scores reclassified patients significantly (overall category-free net reclassification improvement of 31.6 (95% CI, 14.3-49.0; p < 0.0005) mainly by down-classifying those without endpoints.


The authors concluded that ProSP levels post-AMI are prognostic for death, recurrent AMI, or HF, and they improve risk prediction of GRACE scores.


This study reports that ProSP was associated with cardiovascular outcomes such as death, recurrent AMI, and HF rehospitalization. Existing biomarkers such as N-terminal pro–B-type natriuretic peptide mainly predicted mortality and HF, with poorer detection of death and/or reinfarction. In contrast, ProSP provided independent prognostic information for the composite of MACE, death and/or reinfarction, and also death and/or HF. Although, this analysis suggests that SP may potentially have a role in the pathophysiology of outcomes post-AMI, these findings are based on a population from a single center, with two admitting hospitals, and should be verified in other larger populations.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: Risk, Myocardial Ischemia, Myocardial Infarction, Follow-Up Studies, Substance P, Proportional Hazards Models, Death, Biological Markers, Heart Failure, Glomerular Filtration Rate, Hospitalization, Hypertension, Diabetes Mellitus, Natriuretic Peptide, Brain

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