The prognostic value of exercise testing: Exercise capacity, hemodynamic response, and cardio-metabolic risk factors

Treadmill exercise testing is widely available and has been used for more than half a century for the evaluation of exercise related symptoms and assessment of myocardial ischemia. Over the years, additional use and goals for exercise testing have been evolved, including exercise prescription, evaluation of physical capacity and effort tolerance, as well as assessment of arrhythmias, chronotropic competence, and therapeutic response to medications and implanted device interventions.1 With time, it became apparent, that apart from the diagnostic value of the exercise electrocardiogram (ECG) for identification of coronary artery disease and assessment of its severity, aerobic exercise capacity has significant prognostic importance and may aid in the assessment of future cardiovascular risk. The association between low exercise capacity and reduced long-term survival was shown to be independent of traditional risk factors.2 A single measurement of fitness significantly improves classification of both short-term and long-term (25-year) risk for cardiovascular disease mortality when added to traditional risk factors.3 In a meta-analysis of 33 eligible studies of healthy populations a higher level of maximal aerobic capacity amounting to one metabolic equivalent (MET) increase was associated with a 13% risk reduction in all-cause mortality.4 The addition of various imaging modalities to exercise such as myocardial perfusion scans or stress echocardiogram provides greater diagnostic accuracy than exercise ECG testing alone. However, even in today's imaging era, in which modern techniques such as coronary artery calcium scoring and computerized tomography (CT) angiography present high diagnostic and prognostic yield, exercise capacity remains an important predictor of outcomes. Cardiorespiratory fitness, based on percentage of predicted METs achieved during maximal exercise testing, was shown to provide additive prognostic information in type 2 diabetics, beyond that obtained from standard risk scores and coronary artery calcium scoring.5 Similarly, the addition of exercise capacity to the systematic coronary risk evaluation (SCORE) risk model was shown to significantly increase the accuracy of prediction of all-cause mortality among asymptomatic healthy individuals.6 However, despite its well-established prognostic value and the ability to reclassify risk, cardiorespiratory fitness is not incorporated routinely in risk prediction models and assessment tools.7 The prognostic significance of exercise testing extends beyond exercise capacity. Chronotropic incompetence, defined as the inappropriate heart-rate response during exercise or metabolic demand, is predictive of cardiac events and all-cause death.8 Decreased heart-rate recovery is also a strong independent adverse prognostic marker in various patient populations, regardless of exercise protocol used.9,10 In addition, blood pressure response to exercise and recovery has important predictive implications. A decline in systolic blood pressure during exercise may be seen in various clinical scenarios including aortic outflow obstruction, severe left ventricular dysfunction, and myocardial ischemia and, accordingly, is a marker of increased risk for adverse events.11 On the other hand, an exaggerated blood-pressure response to exercise could indicate left ventricular hypertrophy and is correlated by itself with cardiovascular outcomes. Ventricular ectopy during exercise and recovery may also be a predictor of death, and the morphology of exercise-induced ventricular arrhythmia is debated for its prognostic importance.12,13 Overall, studies have shown that there is a graded continuum of risk and additive prognostic effect with the increase in the number and different combinations of abnormal exercise testing parameters and heart-rate-related measures.14–16 In this issue of the European Journal of Preventive Cardiology, Chrysohoou et al. aim to investigate the differential association of exercise testing related parameters with cardio-metabolic risk factors including diabetes, obesity, hypertension, as well as smoking.17 The authors display numerous correlations between cardiovascular risk factors and exercise testing parameters that reflect inotropic and chronotropic response and exercise capacity; these factors include blood pressure and heart-rate reaction during exercise and recovery, exercise duration, and peak METs achieved. The authors suggest that individuals with various risk profiles present different hemodynamic responses during treadmill exercise testing, which may reflect independent pathophysiological pathways. The cross-sectional nature of the study, and the overlapping multiple associations between the risk factors assessed and the exercise related parameters, limit what can be concluded from the study results. Moreover, all of the cardiovascular risk factors were correlated with reduced-exercise tolerance, especially in the younger participants, and clustering of the risk factors was associated with stepwise increase in the probability of diagnosing ischemia during the exercise tolerance test. In addition, the Hellenic SCORE (the Greek adaptation of the European Society of Cardiology SCORE for assessment of 10-year risk for fatal cardiovascular events) independently predicted changes in hemodynamic parameters across exercise. Accordingly, the current study raises the hypothesis, but does not provide the underlying evidence, that differential hemodynamic responses during exercise testing reflect independent pathophysiological pathways. The association between cardiovascular fitness, hemodynamic response, and adverse cardiovascular outcomes is in part modulated through traditional cardiovascular risk factors. In a middle-aged healthy population, low fitness was associated with a higher burden of cardio-metabolic risk factors such as diabetes, hypercholesterolemia, and obesity.18 A long duration of diabetes, for example, may be complicated with cardiac autonomic neuropathy which impairs autonomic control of the cardiovascular system, resulting in abnormal heart rate and blood-pressure response to exercise.15 However, the protective effects of exercise on cardiovascular disease are probably beyond the modification of traditional risk factors.19 Exercise enhances parasympathetic tone, augments heart-rate variability, and improves baroreflex and autonomic function. In addition, vascular adaptations occur with improved endothelial function and increase in compliance of conductive vessels. In response to routine exercise, cardiac remodeling with cellular and molecular adaptations occurs, influencing the structure, function, and electrical stability of the heart.20 Routine physical activity and avoidance of sedentary behaviors are associated with reduced cardiovascular morbidity and increased longevity.21 In today's environment, in which occupation-related and leisure-time physical activity rates are consistently reduced, investigating the reciprocal interactions between cardio-metabolic risk factors and hemodynamic response to exercise is important for understanding and promoting the benefits of exercise in health and disease. The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author received no financial support for the research, authorship, and/or publication of this article.