Risk Stratification in Acute Coronary Syndromes

Abstract & Commentary

By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
This article originally appeared in the November 2006 issue of Clinical Cardiology Alert. It was peer reviewed by Rakesh Mishra, MD, FACC. Dr. Mishra is Assistant Professor of Medicine, Weill Medical College, Cornell University; Assistant Attending Physician, NewYork-Presbyterian Hospital. Dr. Mishra reports no financial relationship relevant to this field of study.

Synopsis: ECG ST depression was strikingly predictive of outcomes in ACS patients, compared to new biomarkers.

Source: Westerhout CM, et al. Short- and long-term risk stratification in acute coronary syndromes: The added value of quantitative ST-segment depression and multiple biomarkers. J Am Coll Cardiol. 2006:48:939-947.

New biomarkers are pushing for a place in our risk stratification of acute coronary syndromes. Their role, as compared to clinical characteristics of the patients and the venerable ECG, is unclear. Hence, Westerhout and colleagues evaluated the GUSTO-IV database to assess the role of ECG ST changes, troponin, C-reactive protein (CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in 7800 patients with non-ST elevation acute coronary syndrome (ACS) in predicting outcomes. Patients were eligible for GUSTO-IV if, within 24 hours of ischemic chest pain, they had an elevated troponin or new ST-segment depression (≥ 0.5 mm). Although the trial was designed to compare abciximab to placebo, since abciximab did not change outcomes, all the patients were considered for this analysis. Coronary angiography was withheld until 12 hours after the study infusion, and additional therapy was at the managing physician's discretion.

The primary end points were 30-day death or myocardial infarction (MI) and one-year mortality. The 30-day death rate was 4%, and 4.5% more died by one year. The 30-day death or MI rate was 8%. The baseline biomarkers, the magnitude of ST depression and heart rate, were all higher in those with events in 30 days or 1 year. Although 13 factors contributed to the 30-day mortality risk, ECG ST depression contributed most to the predictive model; next were creatinine clearance and troponin. Other factors including NT-proBNP were less predictive. However, NT-proBNP was a powerful predictor of one-year death, but was not more predictive than the ECG. CRP was only predictive of one-year death. Westerhout et al concluded that the magnitude of ECG ST depression was strikingly predictive of outcomes in ACS patients, compared to new biomarkers and old measures such as creatinine clearance.


This study illustrates that for the critical 30-day death or MI prediction, the initial ECG is king, especially if it is quantitated, followed closely by troponin. These findings probably explain the utility of the TIMI score, which includes both these factors. Among the newer or non-traditional markers, creatinine clearance was most useful and NT-proBNP was of some value, but CRP did not contribute. Thus, markers of the extent of ischemic injury (ECG and troponin) were the most important for predicting 30-day death or MI, and should be strongly weighted in clinical decisions involving ACS patients.

One-year mortality was also best predicted by initial ECG changes; almost as well was creatinine clearance, closely followed by troponin and NT-proBNP. CRP added to the prediction, but was only 3% of the model as compared to 10% by NT-proBNP. Patients with ECG changes could be sicker, but these results held up when adjusted for baseline characteristics. Creatinine clearance emerged as a powerful predictor, number 3 for 30-day outcomes and second for one-year death, despite the fact that those with severe renal dysfunction were excluded from the study. NT-proBNP correlated best with death at any time point. Surprisingly, CRP performed least well, adding nothing to the prediction of 30-day events and a small amount to one-year mortality.

Westerhout et al developed their own score based upon 7 factors: age, body weight, heart rate, creatinine clearance, ST depression, troponin, and NT-proBNP. However, it is not a simple 7-point score like the TIMI score because each factor is divided into 3 quantitative levels, with different weighted points for each, such that the maximum score is 39-51 depending on the outcome being predicted. Clearly, this is too complicated to ever catch on clinically, but the list of factors is different from others; only 3 are also in the TIMI score. Body weight, heart rate, creatinine clearance, and NT-proBNP are new factors. Thus, creatinine and NT-proBNP should be added to the evaluation of ACS patients.

There are limitations to this study. The ECG and troponin are criteria for admitting the patients to the trial, so there is some bias toward these measures that may not be totally correctable. Reduced renal function may elevate some of the biomarkers confounding these factors. Blood pressure was not evaluated, yet older studies show it has predictive value, especially for death. The study may not be applicable to the general ACS population, as the GUSTO-IV population all underwent cardiac catheterization on their initial admission. Thus, the population is likely higher risk than a more general ACS population. On the other hand, the ECG and troponin will be of value in triaging less sick patients, and useful information can be gained from creatinine and BNP. So, I would use this approach on all potential ACS patients.