American Heart Journal
Volume 144, Issue 5 , Pages 750-752, November 2002

Risk stratification in acute coronary syndromes: The need for continued vigilance in “low-risk” patients☆☆☆

Division of Cardiology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC

Article Outline

Abstract 

Am Heart J 2002;144:750-2.

 

See related article on page 804.

The population of patients with acute coronary syndromes is large and diverse. In the United States alone, there are >5 million visits each year to emergency departments for chest pain, resulting in 2 million admissions and $8 billion in costs.

In approximately 75% of these admissions, however, the diagnosis of an acute coronary syndrome is incorrect.1 Effective risk stratification is required if we are to control costs and limit unneeded admissions, yet reduce the incidence of “missed” myocardial infarctions (MIs).

In 1992, Hamm et al2 reported the first evidence that troponin T could be a useful marker of cardiac necrosis. Troponin T was more sensitive and more specific than creatine kinase (CK)-MB for detection of myocardial injury.3 The persistence of troponin T elevation long after the CK-MB level had returned to normal also allowed the diagnosis of MIs that otherwise would have been missed with the use of CK-MB alone.

The prognostic implications of an elevated troponin T level were extended to patients with unstable angina in the mid-1990s. In one of the first prospective trials addressing this issue, Stubbs et al4 noted significant increases in cardiac death, revascularization, and nonfatal MI in a median follow-up period of 3 years among patients with an elevated troponin T level at baseline. Since then, studies have repeatedly shown that patients with acute coronary syndromes and an elevated troponin level have worse short-term prognoses.5, 6 Despite the substantial evidence that increased troponin levels correlate with short-term risk in acute coronary syndromes, however, substantially fewer studies have focused on the long-term prognosis.7, 8

The 12-lead electrocardiogram (ECG) has always been an essential tool in the evaluation of acute coronary syndromes, along with the patient's history and physical examination. It is inexpensive, readily available, noninvasive, and highly indicative of prognosis. For example, we have long known that patients with acute coronary syndromes and ST-segment elevation have a significantly greater risk of short-term major adverse events such as MI and death.9, 10, 11 More recently, a retrospective analysis of the large Global Use of Strategies To Open occluded coronary arteries in acute coronary syndromes (GUSTO-IIa) trial dataset showed that patients with ST-segment elevation or depression have a higher 30-day risk of death or MI than those with normal ECG results or nonspecific changes.5 Less is known about the prognostic implications of T-wave inversion and other non-ST-segment abnormalities in patients with chest pain, and again, the long-term prognostic implications are unclear.10, 12

Some investigators have examined the relative benefits of using both ECG and troponin information to risk stratify patients with acute coronary syndromes. In GUSTO-IIa, the ECG category and troponin T level each were shown to be complementary and powerful predictors of 30-day mortality rate.5 Overall, 12% of the patients with an elevated troponin T level at baseline had died by 30 days, compared with only 4% of the patients with baseline-negative levels. More important, the troponin T level continued to provide independent prognostic information across all ECG categories, even among patients with ST-segment elevation.5

Jernberg and Lindahl's study13 in this issue of the Journal addresses the realistic integration of the ECG and troponin T level into a single tool for long-term risk assessment of patients with acute coronary syndromes. This study has several notable advantages that increase the “real-world” applicability of the results. First, it reflects a less-studied but critical perspective—the evaluation of patients with acute chest pain in clinical practice. Second, it represents the largest registry of patients with both troponin and ECG information. Third, it followed the patients for substantially longer periods (median, 40 months) than have earlier investigations. Finally, it simplified the point-of-care evaluations by not relying on earlier ECGs. Patients in the United States with acute coronary syndromes often seek care at hospitals outside their usual healthcare environment, which precludes comparisons with earlier ECGs.

Another important aspect of this study is that these observational data are similar to findings from controlled trials, somewhat easing concern about the selection bias that may occur in trials. In Jernberg and Lindahl's study, 24% of the 710 patients had an abnormal troponin T level by 6 hours after admission. Although this is slightly higher than the 10% to 20% of patients in other studies of acute coronary syndromes,7, 8, 14 it likely reflects the advanced age and greater prevalence of earlier coronary disease in their cohort.

Normal ECG results, with strict definitions, were found to be a very favorable prognostic indicator in this study. This finding could be applied to the identification of an elusive cohort, the patients that are truly at low risk for cardiac morbidity and mortality. In an earlier analysis of the same population, the authors showed similar relations between better short-term outcomes and (1) a lack of ST-segment changes on continuous ECG monitoring and (2) a normal baseline troponin T level.15 The combination of the 2 independent predictors of outcome allowed the investigators to divide patients into subgroups with low, medium, and high short-term risk, similar to the current study of longer-term outcomes.

Even among patients with a negative troponin T result and normal ECG results, however, event rates in the median 40-month follow-up period in the study were substantially higher than would be expected. Of note, the risk of death in this cohort was high, regardless of the ultimate diagnosis: 38% of patients with MI, 11% of patients with unstable angina, and 10% of patients with noncardiac or unknown causes of chest pain had died by the end of follow-up. This highlights the continued work that must be done to refine methods of risk stratification in acute coronary syndromes.

We cannot rely on a negative troponin level and normal ECG results alone to capture the full picture of risk among this population. In one study of patients at low risk for cardiac events in a chest pain unit, although 90% of 383 consecutive patients had negative troponin T levels on serial testing, 14% of them had positive stress test results, and 49% were shown to have ≥75% stenosis of at least 1 major coronary artery.7 Furthermore, the 2-year mortality rate was 7%. Supplemental methods of risk stratification are needed.

Perhaps a battery of noninvasive tests and markers should be used, including not only the ECG and CK-MB and troponin levels, but also myoglobin, B-natriuretic peptide, or cobalt-albumin binding, or other methods of measuring ischemia.16, 17 In the recent CHest pain Evaluation by Creatine Kinase-MB, Myoglobin, And Troponin I (CHECKMATE) study, for example, a bedside screening test that included troponin T, myoglobin, and CK-MB levels was a successful means of identifying patients with a poorer prognosis at 30 days.8 Another study has shown that rest perfusion imaging with sestamibi is as good a method of diagnosing MI as serial troponin measurements, and it is a means of identifying patients with significant coronary artery disease.18 We must assess the individual and joint relations of all these variables with short- and long-term outcomes, however, if we are truly to advance the early treatment of patients with chest pain, particularly those with “low” risk for cardiac events.

Although much progress has been made in the ability to risk stratify patients with acute coronary syndromes, we still have much to do. Because of the size of this population, the ability to identify patients who would and would not benefit from early, aggressive treatment would have substantial effects on both resource use and patient outcomes.

The study by Jernberg and Lindahl therefore forms an important link between clinical investigation from randomized trials to the more general practice of cardiology. This registry importantly confirms the observations from clinical trials and sheds light on a new area for further investigation, namely patients who have possibly ongoing ischemia with normal ECG results and negative cardiac markers. Further investigation in this field should prove particularly fruitful.

We have recently initiated a quality improvement program called CRUSADE (Can rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA Guidelines). This registry will collect data on all patients admitted for acute coronary syndromes at >400 hospitals in the United States. The CRUSADE Initiative will examine the use of diagnostic testing, both ECG and troponin testing, and try to identify how this diagnostic strategy works in practice. It is likely that this registry will offer further insight into patients such as those described in this Swedish study. The potential to further enhance our ability to detect ischemia offers a unique opportunity for healthcare providers to improve risk stratification further.

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References 

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☆ Reprint requests: E. Magnus Ohman, MD, UNC-Chapel Hill, Division of Cardiology, 338 Burnett-Womack Building, CB# 7075, Chapel Hill, NC 27599-7075.

☆☆ E-mail: mohman@med.unc.edu

PII: S0002-8703(02)00181-3

doi:10.1067/mhj.2002.126117

Refers to article:

  • A combination of troponin T and 12-lead electrocardiography: A valuable tool for early prediction of long-term mortality in patients with chest pain without ST-segment elevation

    Tomas Jernberg, Bertil Lindahl
    American Heart Journal November 2002 (Vol. 144, Issue 5, Pages 804-810)

American Heart Journal
Volume 144, Issue 5 , Pages 750-752, November 2002

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