There were 6,801 residents of Olmsted County, Minnesota who presented to an ED with an episode of acute chest pain during the study period, January 1, 1985 through December 31, 1992. Of these 2,271 (33.4%) met eligibility criteria and were followed as study subjects. Ineligible patients were excluded for both cardiac and non-cardiac reasons.
Cardiac causes accounted for 4.4% of patients including MI with ST elevation in 3.6% patients, stable angina in 0.7% and aortic dissection in 0.1%. Non-cardiac causes accounted for the exclusion of 40% patients. Another 11.7% patients were excluded because they were non-residents, and 10.4% for other reasons.
The mean age of the cohort upon presentation was 63 years, with 57.5% males and 14.8% with diabetes mellitus (). Using AHCPR criteria, 436 patients (19.2%) were classified as high risk, 1,557 (68.6%) as intermediate risk and 278 (12.2%) as low risk. High-risk patients were more likely to be elderly (<0.001). On applying the TRS to this population, 96 patients were classified as high risk (4.2%), 650 as intermediate risk (28.6%) and 1525 (67%) as low risk. The TRS reclassified over 60% of the patients into a lower risk category compared to their AHCPR classification ().
Baseline Characteristics of the Acute Chest Pain Cohort, by AHCPR Risk Criteria
30 Day Events
Over the first 30 days of follow-up after the qualifying ED visit, 153 (6.7%) patients suffered at least one primary MACCE (). According to the AHCPR criteria, the 30-day event rate was 11.5% in the high-risk group, 6.2% in the intermediate group and 2.5% in the low-risk group (p<0.001). Those in the AHCPR intermediate and high-risk groups with elevated biomarkers (evolving MI) at presentation suffered a higher rate of subsequent events than those without biomarker elevation. Biomarker elevation did not confer additional risk for subsequent events in the low risk AHCPR group since coronary revascularization accounted for all the 30-day events in the AHCPR low-risk group, except for one stroke.
Thirty-Day Events* (Excludes ED Deaths) by AHCPR Category
In univariate logistic regression analysis, the following variables were significantly associated with 30-day MACCE: increasing age, prior MI, prior stable angina, an abnormal index ECG, diabetes mellitus, hypertension, and decreasing systolic blood pressure. All variables except prior MI and diabetes mellitus remained significant in a multiple logistic regression model. Sex, unstable angina, left bundle branch block (LBBB), diastolic blood pressure, hypercholesterolemia, smoking status, and family history were not associated with 30-day events in our study.
During the first phase of long-term follow up at a median of 7.3 years, we observed a MACCE in 1136 patients, 709 of which died. Unadjusted Kaplan Meier survival curves show a reduced cardiac event free survival rate for AHCPR high- and intermediate-risk compared to low-risk patients (). In our cohort, the AHCPR risk score was significantly associated (p<0.001) with follow-up MACCE after adjusting for the following variables. Compared to patients classified as low risk by the AHCPR criteria, both intermediate risk (HR 1.91; 95% CI 1.33–2.75) and high-risk patients (HR 2.45; 95% 1.67–3.58) were significantly more likely to suffer MACCE on long-term follow-up. Age, prior MI, unstable angina, stable angina, diabetes, smoking status, hypertension, an abnormal ECG, LBBB, and systolic blood pressure were all significantly associated with follow-up MACCE. All of these variables except for systolic blood pressure had significant adjusted associations in the multivariable regression model. In the second phase, we observed 1208 deaths over a median follow-up of 16.6 years, translating into a mean annualized mortality rate of 4.7 % for the cohort. Unadjusted Kaplan Meier survival curves show a reduced survival rate for AHCPR highrisk and intermediate-risk compared to low-risk patients. Importantly, for each risk group, survival was similar regardless of whether the patient had an initial elevation of cardiac biomarkers (). After adjusting for other risk factors, high-risk patients demonstrated a 1.68 fold (95% CI 1.13–2.50, p = 0.011) increase in mortality compared to low-risk patients while intermediate-risk patients had a 1.38 fold (95% CI 0.95–2.01, p=0.09) increase in mortality. When the TRS model was added to the multivariable regression model, it did not provide incremental prognostic value either alone (p=0.60) or in combination with the AHCPR classification (p=0.69).
Major Adverse Cardiovascular and Cerebrovascular Events at a Median Follow-up of 7.3 Years
Overall Mortality by AHCPR Risk Level