Methods

The study cohort consisted of patients who presented or were transferred to the University of Michigan Medical Center (Ann Arbor, Michigan) from January 1999 to June 2006 and given the admission diagnosis of acute coronary syndrome. Based on discharge diagnosis, patients with STEMI and unstable angina were then excluded, leaving only patients with NSTEMI. Patients had to present or be transferred within 24 hours of symptom onset. Identified charts were reviewed by physicians for entry criteria. Inclusion into the study required symptoms consistent with acute coronary syndrome and increased cardiac biomarkers (creatinine kinase-MB >2 times upper limit of normal and/or troponin I >0.39 ng/mol for the University of Michigan Medical Center and 0.10 to 2.00 ng/mol for transferred patients). There was no intermediate range for troponin values. Clinical, demographic, treatment, and outcome data were abstracted from medical charts by trained abstractors. Data were collected on a 6-page standardized data form and then forwarded to a database service for dual data entry after review for face validity. Demographic variables included age and gender. Co-morbidities included previous heart disease including angina, congestive heart failure, MI, coronary artery bypass grafting, percutaneous coronary intervention, diabetes mellitus, smoking, hyperlipidemia, and hypertension. Electrocardiographic changes and initial laboratory data were recorded. Procedures and complications during acute coronary syndrome hospitalization were documented. These patients were then followed up by telephone or review of medical records approximately 6 months after discharge, at which point outcomes and medication adherence were noted. The protocol was approved by the institutional review board at the University of Michigan and informed consent was obtained as stipulated by the review board.

All patients with NSTEMI were categorized by FTNMI (n = 659) or first troponin-positive MI (FTNMI; n = 1,196). Univariate comparisons between groups were performed using Pearson chi-square-test or Fisher’s exact test for categorical variables where appropriate and Student’s t test for continuous variables. Multiple logistic regression modeling was performed to derive the independent association of clinical variables with in-hospital outcomes and outcomes at 6 months after discharge. In-hospital outcomes of interest included death, reinfarction, stroke, cardiogenic shock, pulmonary edema, cardiac arrest, atrial fibrillation/flutter, and composite of major adverse cardiac events (i.e., death, stroke, and reinfarction). Reinfarction was defined as re-increase of creatinine kinase-MB or troponin to above upper limits of normal and increase by ≥50% above the previous value. Stroke, embolic and/or hemorrhagic, was defined as onset of focal neurologic signs or symptoms, e.g., loss or slurring of speech, with confirmation by computed tomography or magnetic resonance imaging. Recurrent ischemia was classified as additional symptoms occurring beyond the first 24 hours after presentation combined with electrocardiographic abnormalities and/or increase of cardiac enzyme >2 times upper limit of normal. Cardiogenic shock was defined as presence of pulmonary edema and hypoperfusion characterized by systolic blood pressure <80 mm Hg. We also compared rates of death, recurrent MI, unscheduled revascularization, stroke, and a composite of these at 6 months after discharge. SPSS 15 (SPSS, Inc., Chicago, Illinois) was used for all analyses.

Results

This study included 3,624 consecutive patients who presented with acute coronary syndrome, of whom 1,855 had a NSTEMI. In 659 of the 1,855 patients (35.5%), the first troponin result was negative but later became positive. In 968 of 1,704 patients (56.8%) with NSTEMI with the 2 measurements available, diagnosis was made by troponin increase with creatinine kinase-MB levels <2 times upper limit of normal. Patients with FTNMI were more likely to be men, have a history of transient ischemic attack, and have a history of congestive heart failure. Patients with FTNMI also had fewer T-wave inversions on initial electrocardiogram and a higher presenting mean diastolic blood pressure. Patients with FTNMI were more likely to be taking calcium channel blockers and less likely to be taking clopidogrel on hospital admission. No difference in time to hospital presentation was noted between the 2 groups ( Table 1 ).

As presented in Table 2 , in-hospital cardiac catheterization rates were similar between the 2 groups and coronary artery bypass surgery was more common in patients with FTPMI. Coronary blood flow was significantly different between the 2 groups ( Table 2 ). Thrombolysis In Myocardial Infarction (TIMI) grade 0 to 1 flow was more common in patients with FTPMI and TIMI grade 2 flow was more common in those with FTNMI. No difference existed in mean percent stenosis of the culprit vessel, number of vessels affected, or final mean ejection fraction between the 2 groups.

Pharmacotherapy was different between the 2 groups during hospitalization, at discharge, and at 6 months ( Table 3 ). In-hospital medical treatment showed that patients with FTNMI were more likely to receive unfractionated heparin and less likely to receive statins. On discharge patients with FTNMI were less likely to be on clopidogrel and statins. At 6-month follow-up patients with FTNMI were less likely to be on clopidogrel.

In-hospital symptoms of recurrent ischemia were 2 times as common in patients with FTNMI ( Table 4 ). There were no differences, however, in congestive heart failure, cardiogenic shock, cardiac arrest, stroke, or death in hospital. In addition, time from onset of symptoms to hospital presentation and length of stay were similar between the 2 groups. At 6 months, patients with FTNMI were 2 times as likely to have had recurrent MI ( Table 5 ). The 2 groups did not differ in death, stroke, or cardiac rehospitalization at 6 months. Combined end point of death at 6 months, MI, stroke, and rehospitalization was higher for patients with FTNMI, but this was due to higher rates of recurrent MI.

Table 4

Hospital events

	FTNMI	FTPMI	p Value
Recurrent ischemia	20.1% (132/657)	11.5% (137/1,196)	<0.001
Congestive heart failure	8.4% (55/655)	6.6% (79/1,195)	0.156
Cardiac shock	4.9% (32/655)	4.7% (56/1,196)	0.844
Reinfarction within 24 hours	2.6% (4/155)	3.7% (27/738)	0.505
Cardiac arrest	3.2% (21/657)	2.8% (33/1,195)	0.595
Stroke	0.9% (6/657)	0.6% (7/1,191)	0.423
Death in hospital	4.6% (30/656)	4.5% (53/1,190)	0.906

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