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Diabetes Care 29:1931-1932, 2006
DOI: 10.2337/dc06-0660
© 2006 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Brief Report

Suspected Acute Coronary Syndrome Patients With Diabetes and Normal Troponin-I Levels Are at Risk for Early and Late Death

Identification of a new high-risk acute coronary syndrome population

Steven P. Marso, MD, David M. Safley, MD, John A. House, MS, Todd Tessendorf, MD, Kimberly J. Reid, MS and John A. Spertus, MD, MPH

Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri

Address correspondence and reprint requests to Steven P. Marso, Associate Professor of Medicine, Mid America Heart Institute, University of Missouri-Kansas City, 4401 Wornall, Kansas City, MO 64111. E-mail: smarso{at}saint-lukes.org

Abbreviations: ACC, American College of Cardiology • ACS, acute coronary syndrome • AHA, American Heart Association


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
Clinicians use a variety of methods (1,2) to risk stratify patients with acute coronary syndromes (ACSs). Based on elevated risk, patients are often triaged to an aggressive strategy, including early angiography (3,4) and upstream use of intravenous glycoprotein IIb/IIIa inhibitors (5–7). The current American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Patients with Unstable Angina and Non-ST-segment Elevation Myocardial Infarction do not recognize diabetes as a high-risk ACS indicator. Therefore, we sought to clarify the relative risk of diabetes in early and late death in suspected ACS patients.


   RESEARCH DESIGN AND METHODS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
In this study, a prospective registry of consecutive ACS patients with and without diabetes (n = 864) was used. ACS was diagnosed as either myocardial infarction (8) or unstable angina (9) using standard definitions. Patients with ST-segment elevation myocardial infarction were excluded. All potential unstable angina patients who had a diagnostic angiographic, nuclear, or echocardiographic stress test that excluded obstructive coronary disease or who had an additional diagnostic study confirming an alternative explanation for presentation were excluded. Diabetes was defined by reported history or new antidiabetic therapy initiated during the index hospitalization. Institutional review board approval was obtained, and all patients provided informed consent.

Continuous data are reported as means ± SD. Differences between groups were tested using ANOVA and compared using {chi}2 or Fisher’s exact test. Survival curves were derived by Kaplan-Meier analysis and compared using log-rank tests. Analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC) and R version 1.8.0.


   RESULTS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
There were 864 patients in this registry. There was a measurable difference in mortality at 30 days for diabetic patients compared with nondiabetic patients (1.7 vs. 0.2%, respectively, P = 0.02). Two-year survival rates by diabetes and troponin-I status are illustrated in Fig. 1.


Figure 1
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  		Figure 1— Kaplan-Meyer survival rates at 2 years by diabetes status and troponin level. DM, diabetes mellitus; Tn-I+, troponin I greater than the upper limit of normal; Tn-I-, normal troponin I.

 
The ACC/AHA high-risk features of ACS that were significant multivariable predictors of death at 2 years included rales (hazard ratio 2.5 [95% CI 1.4–4.3], P = 0.002), troponin greater than the upper limit of normal (1.9 [1.1–3.2], P = 0.013), previous myocardial infarction (1.9 [1.2–3.0], P = 0.004), age per 10-year increase (1.5 [1.2–1.8], P < 0.001), and ejection fraction per 1% decrease (1.04 [1.02–1.06], P < 0.001). Diabetes was also a significant predictor (1.8 [1.1–2.7], P = 0.014).

In-hospital angiography was performed less frequently in diabetic patients than in nondiabetic patients (74 vs. 79%, respectively, P = 0.077). Among diabetic patients, 82% with elevated troponin-I levels underwent in-hospital angiography compared with 66% with normal troponin-I levels (P < 0.001). A significantly greater number of diabetic patients with normal troponin-I levels were managed medically (63 vs. 42%, P < 0.001). Administration of glycoprotein IIb/IIIa inhibitors was approximately three times more common in diabetic patients with troponin-I elevation compared with diabetic patients with normal levels (49 vs. 16%, respectively, P < 0.001).


   CONCLUSIONS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
In this series of ACS patients, diabetes was associated with increased risk of short- and long-term mortality. This risk persisted following multivariable adjustment, including the contribution of troponin-I levels and other recognized ACC/AHA high-risk features. We believe these findings confirm the prognostic importance of diabetes in ACS patients and suggest that it be included among the high-risk features of suspected ACS patients in clinical guidelines.

It is currently estimated that the prevalence of diabetes among ACS patients is approaching 50% (10). Physicians assess risk among suspected ACS patients in a variety of ways. Current ACC/AHA guidelines provide comprehensive and evidence-based methods to facilitate assessment, risk stratification, and treatment of ACS patients. However, diabetes is not recognized as a high- or intermediate-risk mediator. Our findings are consistent with others (11,12), although our data extend the risk to patients with diabetes and normal troponin levels.

While we derived our population using strict inclusion criteria, a potential selection bias may have identified a unique population with normal troponin-I levels. Also, new-onset diabetes patients may have been misclassified as nondiabetic, resulting in an exaggerated difference in mortality if duration of diabetes mediates our observed mortality association. Although previous work is conflicting (13), it is plausible that unrecognized diabetic patients have a lower hazard for mortal events.

In this ACS population, diabetes was associated with increased risk of mortality. This difference was notable 30 days after ACS and persisted through 2 years. Although patients with diabetes and elevated troponin-I levels had a significant risk of 2-year death, patients with diabetes and normal troponin-I levels had a risk of death equivalent to patients without diabetes who had elevated troponin-I levels. Diabetes was also associated with risk estimates similar to the currently identified ACC/AHA high-risk ACS features. Patients with diabetes and normal troponin-I levels were less likely to undergo in-hospital angiography and receive medical treatment known to reduce risk. This study suggests that the risk of diabetes is at least equivalent to that of elevated troponin levels and supports the inclusion of diabetes as a high-risk feature in triaging ACS patients.


   Acknowledgments
 
This project was supported in part through a grant from the Agency for Health Care Research & Quality (R-01 HS11282-01).

The authors thank Joseph Murphy and Jose Aceituno for their expert contributions in the preparation of this manuscript.


   Footnotes
 
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

DOI: 10.2337/dc06-0660

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received for publication March 27, 2006. Accepted for publication April 26, 2006.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

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