Effect of Age and End Point on the Prognostic Value of the Exercise Test

doi:10.1378/chest.125.5.1920

Chest

Volume 125, Issue 5, May 2004, Pages 1920-1928

https://doi.org/10.1378/chest.125.5.1920 Get rights and content

Background

The clinical and exercise test variables chosen for predicting prognosis vary in the available studies. This could be due to the effect of age of the patients tested and the choice of outcomes used as end points in these follow-up studies.

Objective

To evaluate the effect of age and end points on exercise test variables chosen as significantly and independently associated with time to death.

Methods

Analyses were performed on the first treadmill test performed on consecutive male veterans at the Palo Alto and Long Beach Veterans Affairs Medical Centers since 1987. After removal of patients with congestive heart failure, coronary interventions, left bundle-branch block, atrial fibrillation, myocardial infarction and/or Q wave, and digoxin use, 3,745 male subjects remained. The outcomes were cardiovascular and all-cause mortality. The study population was divided into subsets according to age; exercise test and clinical variables were analyzed within the age subsets using the Cox hazard model.

Results

The mean age at the time of testing was 57 ± 12 years (± SD) and they were followed up for a mean of 6.6 years. There were 544 all-cause deaths, with 206 of the deaths being due to cardiovascular causes (38%). When the study group was classified into subsets based on age, exercise capacity (in metabolic equivalents [METs]) was chosen by the Cox hazard model most consistently in the age groups using either end point. Even when age was added to the Duke treadmill score, prediction of death did not improve in those > 70 years of age because of the nonlinear relationship between age, the exercise test variables, and time to death. The most important age cut points for clinically important differences in exercise test predictors appeared to be 70 years and 75 years of age. In the patients 70 to 75 years of age, peak METs was the only variable predictive of all-cause mortality, and exercise-induced ST-segment depression was the only predictor of cardiovascular death; in the patients > 75 years of age, none of the exercise test responses were predictive of either death outcome.

Conclusion

Both age and the outcome selected as an end point affect the exercise test responses chosen for scores to predict prognosis. Differences in age of the subjects tested and/or the outcome selected as the end point can explain the differences in the studies using exercise testing to predict prognosis.

Section snippets

Study Population and Data Collection

Consecutive male patients (n = 6,213) referred for exercise tests for clinical indications at two university-affiliated Veterans Affairs (VA) Medical Centers (Long Beach VA from 1987 to 1991 and Palo Alto VA from 1992 to 2000) were considered for analysis. These laboratories were directed in consistent fashion by two of the authors (V.F.F. and J.M.). Both laboratories were affiliated with universities and had academic medical staffs with rotating house officers and fellows. Tests were directly

Population Demographics, Hemodynamic and ECG Responses

Mean follow-up was 6.4 years, during which time 544 all-cause deaths were observed, 206 of which had a cardiovascular cause (38%). Annual mortality was 0.7% for cardiovascular death and 1.8% for all-cause deaths. There were significant differences for nitrate and antihypertensive drug use between the survived and death groups but not for beta-blocker use (Table 1). Those who died were significantly more likely to have pulmonary disease, claudication, typical angina, and hypertension. No

Discussion

Clinical guidelines regarding ischemic heart disease have recommended the standard exercise test as the first choice for the evaluation of the elderly patient without confounding resting ECG abnormalities and that the DTS be used for prognostication.¹⁰ The DTS was derived using infarct-free survival from a cohort of patients admitted for cardiac catheterization with a mean age of 49 years,¹¹ and later validated in outpatients (to lessen workup bias) using all-cause mortality as an end point.¹²

Conclusion

Both age and the outcome selected as an end point affect the exercise test responses chosen for scores to predict prognosis. Differences in either age of the subjects tested and the outcome selected as the end point can explain the differences in the studies using exercise testing to predict prognosis. The possibility that the exercise test does not have prognostic value in men > 75 years of age has such clinical importance that research using a prospective design avoiding the limitations of

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Cited by (7)

Age and Double Product (Systolic Blood Pressure × Heart Rate) Reserve-Adjusted Modification of the Duke Treadmill Score Nomogram in Men
2008, American Journal of Cardiology
Citation Excerpt :
Differences in physiological responses to exercise appear with aging19–21 but age was not originally incorporated into the DTS, probably due to the narrow age range of the patient population from which the DTS was developed. Previous studies have evaluated the effect of age on the prognostic value of the exercise test7,22 and the additional prognostic information of hemodynamic variables such as HR recovery.23 The present study, however, extends previous findings in several respects.
The Duke Treadmill Score (DTS) is an established clinical tool for risk stratification. Our aim was to determine if other variables could improve the prognostic power of the DTS and if so, to modify the DTS nomogram. From a total of 1,959 patients referred for exercise testing at the Palo Alto VA Medical Center from 1997 to 2006 (a mean follow-up of 5.4 years), we studied 1,759 male veterans (age 57 ± 12 years) free of heart failure. Double product (DP) was calculated by multiplying systolic blood pressure and heart rate; variables and their products were subtracted to obtain the differences between at rest and maximal exercise (reserve) and recovery. Of all the hemodynamic measurements, DP reserve was the strongest predictor of cardiovascular death (CVD) (Wald Z-score −3.84, p <0.001) after adjustment for potential confounders. When the components of DTS were entered in the Cox hazard model with DP reserve and age, only DP reserve and age were chosen (p <0.00001). Using the Cox coefficients, a score calculated by [age − DTS – 3 × (DP reserve/1,000)] yielded an area under the curve of 0.84 compared with 0.76 for the DTS. Using this equation, a nomogram was constructed by adding age and DP reserve to the original DTS nomogram improving estimation of annual CVD. In conclusion, we propose an age and DP reserve-adjusted DTS nomogram that improves the prognostic estimates of average annual CVD over the DTS alone.
Age-adjusted modification of the Duke Treadmill Score nomogram
2008, American Heart Journal
Citation Excerpt :
Although the DTS is generally considered to be effective for stratification of patients with ischemic heart disease into appropriate diagnostic and prognostic categories, the addition of other prognostic covariates may increase its predictive accuracy. Despite the prognostic significance of age for cardiovascular mortality,18,27,28 it was not incorporated into the DTS, most likely due to the limited age range of the patient population from which the DTS was developed. In our study population, age was at least as strong a prognostic predictor as the DTS.
The Duke Treadmill Score (DTS) is an established clinical tool for risk stratification of patients referred for exercise testing, but it does not consider age. We aimed to determine if age could improve the prognostic power of the DTS and if so, to modify the DTS nomogram to include age.
Of 1,959 patients referred for exercise testing from 1997 to 2006, 1,759 male veterans (age range 23-86 years) remained after exclusion of female and patients with heart failure. Cardiovascular mortality was the main outcome considered.
Cox survival analysis was performed entering age and the DTS; both were significant (P ≤ .002) with similar Wald Z values (5.4 and −3.1) and regression coefficients but opposite signs. The score: age–DTS yielded an area under the receiver operating characteristic curve of 0.80 compared with 0.76 for the DTS (P < .001). Using this equation, a nomogram was constructed by adding age to the original DTS nomogram. The point at which the age–DTS line intersects the drawing line from the DTS to the corresponding value for age indicates average annual cardiovascular (CV) mortality adjusted for age. For a DTS associated with a 2.5% annual CV mortality, an age of 30 compared with 70 decreased CV risk by a factor of 10 to less than 0.2% (P < .05, log-rank test).
We propose an age-adjusted DTS nomogram that improves the prognostic estimates of average annual CV mortality over the DTS alone. This nomogram requires external validation and extension to women.
A new scoring system for evaluating coronary artery disease by using blood pressure variability
2017, Australasian Physical and Engineering Sciences in Medicine
Preoperative evaluation of the adult patient undergoing non-cardiac surgery: Guidelines from the European Society of Anaesthesiology
2011, European Journal of Anaesthesiology
Augmented blood pressure response to exercise is associated with improved long-term survival in older people
2009, Heart
Relationship of predictive modeling to receiver operating characteristics
2008, Journal of Cardiopulmonary Rehabilitation and Prevention

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Chest

Exercise and the HeartEffect of Age and End Point on the Prognostic Value of the Exercise Test

Background

Objective

Methods

Results

Conclusion

Section snippets

Study Population and Data Collection

Population Demographics, Hemodynamic and ECG Responses

Discussion

Conclusion

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Card Fail

Am J Med

J Am Coll Cardiol

Chest

J Am Coll Cardiol

Exercise and the Heart.

Data management: a better approach

Physicians Comput

Exercise and the Heart
Effect of Age and End Point on the Prognostic Value of the Exercise Test