From the 1Denver Health Medical Center

Exercise treadmill testing is frequently used in clinical practice to obtain valuable diagnostic and prognostic information. Multiple measures acquired during this test, including exercise capacity, contribute to the overall interpretation of the test. The prognostic value of exercise capacity in predicting mortality has been well established.

 Little is known, however, about the role of exercise capacity in predicting nonfatal cardiac events.

Our objective was to evaluate the prognostic importance of exercise capacity for predicting nonfatal cardiac events, independent of other parameters measured during exercise treadmill testing among patients referred for this test for clinical reasons. The study was designed to clarify the significance of reduced exercise capacity for clinicians interpreting

exercise treadmill test results in clinical practice.

Exercise capacity was a strong and independent predictor of nonfatal cardiac events in a community cohort of patients referred for exercise treadmill testing. This study suggests that exercise capacity independently identifies patients at higher risk for cardiovascular events. While prospective studies are needed to determine the optimal diagnostic and therapeutic approaches for these patients, clinicians should consider aggressive risk-factor modification and close follow-up in those with impaired exercise capacity.

We used a retrospective cohort study design, enrolling 9191 consecutive patients referred for exercise treadmill testing in a large managed care organization. Symptom-limited treadmill testing was performed according to standardized protocols. Exercise capacity was defined as the proportion of the age- and sex-predicted metabolic equivalents achieved

and was categorized as less than 85%, 85% to 100%, and greater than 100%.

Classification of Diseases, Ninth Revision, Clinical Modification

The primary outcomes of myocardial infarction (MI), unstable angina, and coronary revascularization procedures, defined as either coronary artery bypass graft surgery or percutaneous coronary intervention, were identified using primary discharge diagnosis 

) codes. All-cause mortality was evaluated as a secondary outcome.

Outcomes across levels of exercise capacity were compared using the Kaplan-Meier method, and differences in event rates were evaluated with the log-rank test. The independent prognostic importance of exercise capacity for nonfatal cardiac events was assessed using multivariable Cox proportional hazards regression. We adjusted for demographics, indication for treadmill testing, comorbidities, and several exercise treadmill testing measures, including heart rate recovery, chronotropic incompetence, ventricular ectopy in recovery, ST-segment deviation, and chest pain during exercise. Finally, the relationship between exercise capacity and nonfatal cardiac events was explored in prespecified patient subgroups.

Patients with lower exercise capacity were more likely to be women, to smoke, and to have a higher body mass index and more comorbid conditions, such as diabetes and hypertension. With regard to other exercise treadmill test measures, patients with reduced exercise capacity were more likely to have chest pain upon exercising, ST-segment changes, abnormal heart rate recovery, and an abnormal chronotropic index.

Over a mean of 2.7 years of follow-up, rates of MI, unstable angina, and coronary revascularization were greater among those with lower exercise capacity (log rank, 

<.01 across levels of exercise capacity for each outcome; 

). After accounting for demographic, clinical, and exercise treadmill test measures, lower exercise capacity remained strongly associated with an increased risk of MI (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.55-3.60), unstable angina (HR, 2.39; 95% CI, 1.78-3.21), and coronary revascularization (HR, 1.75; 95% CI, 1.46-2.08) for those who achieved less than 85% of their predicted exercise capacity compared with those who achieved more than 100% (

 Those achieving 85% to 100% of their predicted exercise capacity did not have a significant increase in risk of nonfatal outcomes compared with those who achieved more than 100%. Finally, the association between exercise capacity and each of the outcomes was consistent in all patient subgroups evaluated (

Exercise capacity was also independently associated with an increased risk of all-cause mortality. This was true for those who achieved less than 85% (HR, 2.90; 95% CI, 1.88-4.47) of their predicted exercise capacity and for those achieving 85% to 100% (HR, 1.78; 95% CI, 1.13-2.81) compared with those who achieved greater than 100% (Table).

In this community-based population of patients referred for exercise treadmill testing for clinical indications, patients with a decreased exercise capacity had an increased risk of MI, unstable angina, and coronary revascularization; this finding was independent of patient characteristics and other exercise treadmill test parameters. Failure to reach 85% of age- and sex-predicted metabolic equivalents was associated with a 2.4-fold higher risk of MI, a 2.4-fold higher risk of unstable angina, a 1.8-fold higher risk of revascularization, and an almost 3-fold higher risk of death from all causes.

The primary finding of this analysis is that exercise capacity predicts future cardiac events. Prior studies have not focused

specifically on the utility of exercise capacity for predicting future nonfatal cardiac events in patients referred for exercise treadmill testing. While poor exercise capacity is generally considered a maker of a poor prognosis, this association is often attributed to other comorbidities. Various conditions can result in reduced exercise capacity, such as chronic lung disease, arthritis, and musculoskeletal disorders. Clinicians interpreting exercise treadmill tests might assume that future adverse outcomes are related to such conditions, thereby underestimating the risk of future cardiac morbidity, particularly in the absence of other treadmill indicators, such as chest pain or ST-segment changes. We found that patients with reduced exercise capacity have an increased risk of subsequent nonfatal cardiac events, independent of other comorbidities and traditionally reported exercise treadmill test measures, such as ST-segment deviations and chest pain. Exercise capacity, therefore, is an important indicator of cardiovascular risk and not simply a less specific indicator of a greater burden of comorbidity.

Because multiple exercise treadmill test measures have prognostic significance and should be incorporated in the assessment of prognosis,

 it is important to understand the prognostic value of exercise capacity independent of the contribution of other measures. This study demonstrates the predictive value of exercise capacity for nonfatal cardiac events independent of other exercise testing measures, including chest pain, ST-segment changes, heart rate recovery, chronotropic index, and ventricular ectopy in recovery. Although other studies have shown that reduced exercise capacity is associated with higher mortality rates,

 none of these adjusted for all exercise treadmill test parameters independently associated with survival, such as chronotropic index and heart rate recovery.

Reduced exercise capacity may be useful in clinical practice to identify high-risk patients who may benefit from therapeutic interventions. Prospective studies are needed to determine the best approach for these patients; however, aggressive risk-factor modification and close follow-up should be considered to reduce the risk of future cardiac events. Given the magnitude of the association, further evaluation of the benefits of aggressive diagnostic and therapeutic strategies directed at preventing cardiac events in patients with reduced exercise tolerance is warranted. Physical activity is also known to improve exercise tolerance and reduce the risk of adverse outcomes.

 Finding poor exercise tolerance on exercise treadmill testing may provide clinicians with an opportunity to discuss the benefits of physical activity and encourage sedentary patients to increase their level of physical activity.

Our study had several limitations. First, exercise capacity was estimated on the basis of the speed and degree of incline of the treadmill and not directly measured using ventilatory gas exchange.

 Achieved metabolic equivalents, however, are standardized and are an objective measure of exercise capacity in clinical practice. Second, the generalizability of the results may be limited because the study population came from a single managed care organization. Finally, the results may be affected by unmeasured confounding variables; however, a large number of covariates were included in the multivariable models, including comorbid conditions and extensive treadmill variables.

Exercise capacity was a strong and independent predictor of nonfatal cardiac events in a community cohort of patients referred for exercise treadmill testing. This study suggests that exercise capacity independently identifies patients at higher risk for cardiovascular events. While prospective studies are needed to determine the optimal diagnostic and therapeutic approaches for these patients, clinicians should consider aggressive risk-factor modification and close follow-up in those with impaired exercise capacity. 

The authors have no relationship with any commercial entity that might represent a conflict of interest with the content of this article.

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Reduced exercise capacity is associated with an increased risk of myocardial infarction, unstable angina, and coronary revascularization in patients referred for exercise treadmill testing for clinical indications.

From the 1Denver Health Medical Center

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