Pro-substance P levels predicted events after acute MI

Levels of pro-substance P, a stable surrogate marker for labile substance P, predicted death, recurrent acute MI and HF in patients with acute MI, according to a new study.

Pro-substance P levels also improved the risk prediction of Global Registry of Acute Coronary Events (GRACE) scores, chiefly by down-classifying risk in people without events, researchers found.

Substance P is known to have proinflammatory effects, to increase platelet aggregation and clot strength and to reduce fibrinolysis, according to the study background.

Leong L. Ng, MD, and colleagues investigated whether pro-substance P was associated with poor prognosis after acute MI. They measured pro-substance P in 1,148 patients with acute MI (825 men; mean age, 66.2 years). The endpoints studied were major adverse cardiac events, a composite of death, reinfarction and hospitalization for HF; death or reinfarction; and death or HF. The researchers also compared GRACE scores with pro-substance P for death and/or reinfarction at 6 months.

At 2 years, Ng, of the department of cardiovascular sciences at the University of Leicester, Glenfield Hospital, Leicester, United Kingdom, and colleagues observed 140 deaths, 112 hospitalizations for HF and 149 reinfarctions.

They found that pro-substance P levels were highest on the first 2 days after admission and were related to estimated glomerular filtration rate, age, diabetes status, ischemic heart disease or hypertension, Killip class, left ventricular wall motion index and sex.

Predictor of events

Using multivariate Cox regression models, they determined that pro-substance P level was a predictor of major adverse cardiac events (HR=1.3; 95% CI, 1.1-1.54), death or reinfarction (HR=1.42; 95% CI, 1.2-1.68) and death or HF (HR=1.38; 95% CI, 1.14-1.67).

Ng and colleagues found that both pro-substance P levels and GRACE scores were independent predictors of death and/or reinfarction at 6 months (P<.0005 for both). When pro-substance P levels were added in to the GRACE score, it significantly improved reclassification of patients (overall category-free net reclassification improvement, 31.6; 95% CI, 14.3-49), primarily by down-classifying patients without endpoints, according to the researchers.

At 6 months, those with pro-substance P levels <72.08 pmol/L and GRACE score <137 had an event rate of just 3%, whereas those with pro-substance P levels >121.6 pmol/L had a death rate of 30.7% and a death or recurrent acute MI rate of 37.7%, Ng and colleagues wrote.

Christopher B. Granger

A long journey

Christopher B. Granger, MD, of Duke Clinical Research Institute, and Thomas J. Povsic, PhD, of Duke University Medical Center, wrote in a related editorial that the study’s strengths include identification of a novel biomarker and demonstration of its addition to predictive capability, but its weaknesses include its single-center nature and the lack of an independent validation cohort.

“There is a major need to distill the vast information in biomarkers with initial proof of concept, such as pro-substance P, but then, translating that information into clinical tools to guide and improve care is the most challenging part of clinical risk marker development,” Granger and Povsic wrote. “Although the work of Ng et al is a first step, it is a long journey.”

For more information:

Granger CB. J Am Coll Cardiol. 2014;64:1708-1710.

Ng LL. J Am Coll Cardiol. 2014;64:1698-1707.

Disclosure: The study was sponsored by the John and Lucille Von Geest Foundation and the National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit. See the full study for the researchers’ relevant financial disclosures. See the full editorial for Granger’s relevant financial disclosures. Povsic reports no relevant financial disclosures.