Blood pressure responses during exercise testing—is up best for prognosis?

Abstract

Exercise testing is not limited to observation of ischemic electrocardiographic findings during exercise, but also abnormal findings in blood pressure, heart rate, and exercise capacity are valuable.

Individuals with exaggerated exercise blood pressure tend to develop future hypertension. Extensive elevation in systolic blood pressure during exercise has been found to increase the risk of left ventricular hypertrophy, myocardial infarction, cerebrovascular stroke, and cardiovascular death. Previous studies have revealed that blood pressure response to exercise is dependent on underlying heart disease and peripheral resistance. Therefore, subjects with documented cardiovascular disease may not be capable of generating a work-load to allow the manifestation of exercise-induced systolic hypertension. Systolic hypotension during exercise is associated with left ventricular dysfunction and inadequate cardiac output, and it is a marker of severe heart disease.

Exercise testing with the definition of blood pressure can be performed in a logical way with test results used to decide on therapies and treatment strategies in addition to blood pressure at rest. A modest increment in blood pressure rise corresponding to work-load achieved during the exercise testing is the best sign from the prognostic point of view. The normal limits of exercise blood pressure response could be very helpful for clinicians.

Key words::

• Blood pressure
• cardiovascular disease
• exercise testing
• prognosis

Abbreviations
CHD	=	coronary heart disease
CVD	=	cardiovascular disease
ECG	=	electrocardiogram
SBP	=	systolic blood pressure

Key messages

• The assessment of blood pressure during exercise testing may give additional information to ambulatory blood pressure defined at rest.

• Individuals with exaggerated exercise blood pressure tend to develop future hypertension.

• The limits of normal exercise blood pressure could be very helpful for clinicians when a decision about the treatment strategies is to be made

Introduction

Modern exercise testing is not limited to observation of ischemic electrocardiographic (ECG) findings during exercise, but also abnormal findings in blood pressure, heart rate, and exercise capacity are valuable. Systolic blood pressure (SBP) changes according to work-loads during an exercise test correspond to blood pressure responses in daily physical stress conditions (1). The assessment of blood pressure during clinical exercise testing may give additional information to ambulatory blood pressure normally defined at rest. However, in current clinical practice, it is not clearly shown how blood pressure measurements should be taken into account when exercise test findings are reported. Blood pressure decrement during exercise is a previously accepted prognostic and diagnostic finding. Systolic hypotension during exercise is usually associated with left ventricular dysfunction and inadequate cardiac output, and it is a marker of very severe coronary heart disease (CHD) and in association with other measures of ischemia predicts a poor prognosis, with a high positive predictive value for left main or multi-vessel coronary artery disease (2).

The predictive value of blood pressure response as a risk marker for future cardiovascular disease (CVD) may be dependent on two main reasons including the differences in exercise testing protocol and the patient's clinical status. Firstly, it is well known that exercise testing protocols may vary, and, secondly, blood pressure response to exercise may be different among those without evidence of previous CVD as well as patients who have already documented heart disease.

Cycle and treadmill are two commonly used exercise testing methods. Treadmill exercise is generally the preferred modality in the United States. It is argued that some untrained subjects will terminate cycle exercise because of quadriceps muscle fatigue. However, several studies have demonstrated a consistent relationship between exercise capacity on treadmill and cycle ergometer (3). One of the strengths is that with the cycle ergometer it is easy to obtain reliable measurements of blood pressure as compared to treadmill exercise protocols. Clinical exercise testing protocols lasting about 10 minutes are recommendable to avoid great variability in blood pressure response (4). The results showing the predictive the role of a rise in SBP during exercise should be generalized with caution, as some studies use different exercise testing protocols (5). The normal values during cycle exercise testing among middle-aged subjects are shown in Figure 1. It remains to be seen whether findings would be applicable to various exercise test protocols using submaximal or maximal exercise for the definition of exercise blood pressure. The standardized measurements for blood pressure during exercise testing are necessary for the evaluation of CVD risk.

Figure 1. An average systolic blood pressure response during symptom-limited cycle exercise testing with a 20-watt increment in work-load every 1 minute. Reproduced from Kurl S, Laukkanen JA, Rauramaa R, Lakka TA, Sivenius J, Salonen JT. Systolic blood pressure response to exercise stress test and risk of stroke. Stroke. 2001;32(9):2036–41 (5).

It is not well known whether treatment of elevated exercise SBP alters the progression of the underlying physiological abnormalities in hypertension or improves the outcome. However, exercise testing can be used to identify persons with exaggerated systolic blood pressure response during and after exercise, indicating future risk for developing hypertension and increased mortality.

Blood pressure definition during exercise

The monitoring of blood pressure at each incremental work-load and during recovery is an essential part of exercise testing, although it is not very easy to detect to Korotkoff sounds during exercise. Systolic blood pressure is generally easier to define than diastolic blood pressure during exercise (6). During dynamic exercise, mean blood pressure differences between intra-arterial and non-invasive determinations are quite similar to those at rest. Systolic blood pressures recorded intra-arterially and by sphygmomanometer have been similar during exercise (6). It is sometimes difficult to obtain an accurate definition of SBP due to body movements related to high level of exercise at maximal effort (7). Exercise blood pressure can be measured automatically or manually by the cuff stethoscope method when a subject is sitting on the cycle ergometer or walking on a treadmill exercise. Blood pressure can be usually measured every 2 or 3 minutes during the exercise test.

Blood pressure during exercise is dependent on cardiac output and peripheral resistance. Resting cardiac output (5 to 6 L/minute) increases to as high as 20 to 25 L/minute during peak exercise, an increase proportional to the exercise work-load. A heart that can function well when ejecting against very high resistance during exercise is usually fairly well perfused. In response to the increased stroke volume and systolic contractile force, SBP normally rises with increasing work-loads. As exercise progresses, SBP increases typically by 50–70 mmHg, whereas diastolic blood pressure remains almost unchanged as a result of vasodilatation and a decrease of total peripheral resistance (4). When cardiac output is not balanced by increased compliance from peripheral muscle vasculature dilation, the result is a sharp increase in SBP (8). This aberrant physiology, which may relate to early vascular stiffness or an exaggerated sympathetic response, may account for the increased risk.

Resting SBP is a major determinant of maximal SBP during exercise. Maximal SBP has been found to be higher in hypertensive patients. Age, gender, body-weight, cardiorespiratory fitness, and cardioactive medication have been shown to affect the blood pressure response to exercise (9). The total rise in SBP has been lowest among older and hypertensive persons as well as subjects with CHD. On the other hand, subjects with higher blood pressure during exercise in younger ages may have elevated blood pressure later in life. In a recent study, authors found that CVD risk factors would have an influence on blood pressure response during exercise in children and adolescents (10).

Blood pressure responses and the risk of cardiovascular diseases

It would be very useful to determine what kind of blood pressure responses can be seen as normal blood pressure response among an aged population with or without previous CVD. A recent study by Hedberg et al. increases our knowledge about the value of exercise blood pressure among a community-based sample of older subjects (11). This study shows the prognostic value of SBP change from rest to peak exercise during symptom-limited cycle exercise test. The authors found that exercise SBP change of over 55 mmHg was related to decreased risk of overall mortality as compared to those who had exercise SBP change of less than 33 mmHg. One of the strengths was that they also measured ejection fraction showing that subjects had a normal ejection fraction at rest and there were no marked differences in ejection fraction according to exercise SBP changes, although the average exercise capacity was quite low from 106 to 110 W (6.3 to 6.9 METs) among non-survivors and survivors. Among consecutive patients who underwent symptom-limited exercise testing, an increment in SBP of at least 44 mmHg during exercise testing was associated with an improvement in survival (12). In our previous study we found that middle-aged men with a moderate increase in SBP (36 to 63 mmHg) during bicycle exercise had a lower rate of myocardial infarction whereas those with very high SBP increase had increased risk of myocardial infarction (13). The important difference between these studies is that among younger subjects without previous CHD an average SBP rise is higher than among older subjects (11–13). On the basis of previous studies, it seems that very steep or abnormally low SBP reactions are related to an increased risk of cardiovascular outcomes, indicating U- or J-shaped associations between cardiovascular risk and the SBP response to the standardized cycle exercise testing protocol consisting of a progressive increase in the work-load.

Exercise capacity may cause variation in SBP response to exercise. Fit subjects may have higher maximal SBP and higher total SBP rise with increasing work-loads due to their better exercise capacity (14). Normally, trained subjects achieved a significantly higher maximal SBP compared with untrained subjects during exercise. Fit subjects showed a slower rate of rise of SBP during the first stages of exercise as compared with the unfit groups. The higher SBP in trained individuals is a normal adaptive response that is due to increased cardiac output and may be required to vital organs under the conditions of low systemic vascular resistance, while in the untrained subjects increased total peripheral resistance is the most likely mechanism for high SBP. Increased peripheral resistance during exercise may be an important factor related to the risk of CVD (14).

It is observed that there is an association between diastolic blood pressure during the exercise and cardiovascular events (8). A recent study showed that diastolic blood pressure from submaximal to maximal exercise work-load predicts the risk of CVD death (15). However, the predictive value of diastolic blood pressure during exercise is attenuated once resting blood pressure was taken into account.

Systolic blood pressure during exercise among subject without known cardiovascular disease

Systolic blood pressure changes at different work-loads during an exercise test correspond to blood pressure changes in daily physical stress conditions (1,9). SBP may increase greatly among subjects who did not have diagnosed disease. Exercise-induced elevation in SBP has been found to increase the risk of future hypertension (16,17), left ventricular hypertrophy (18), cerebrovascular stroke (5), and CVD death (19,20). An abnormal rise in exercise SBP in a subject with a normal resting pressure predicts increased risk for future hypertension (17). In an apparently healthy population, a higher exercise blood pressure has been related to resting hypertension or prehypertension and, thus, exercise SBP is associated with long-term adverse prognosis (21).

In addition to these findings, an abnormal rise in exercise SBP in a subject with a normal resting pressure may precede future resting hypertension. An increase of SBP during an exercise test at a moderate work-load predicted better CVD mortality than SBP at rest (19), whereas exercise SBP at moderate work-loads had limited value in the evaluation of CVD risk compared with resting SBP in hypertensive patients (14). In a large prospective study (19), very high exercise-induced elevation of SBP (over 230 mmHg) was related to an increased risk of death from CVD showing the evidence that an exaggerated response in normotensive subjects may be of prognostic value. In asymptomatic individuals, elevated exercise blood pressure carried higher risk of CVD death but became non-significant after accounting for blood pressure at rest (15). However, treadmill exercise testing work-load corresponding to a submaximal level with blood pressure of over 180/90 mmHg identified resting normotensive individuals who had an increased risk of future CVD death. In this study (15), authors reported that base-line hypertension modifies the observed association, suggesting that the predictive role of exercise blood pressure was most important among resting normotensive or border-line hypertensive patients.

Systolic blood pressure during exercise among subjects with previous cardiovascular disease

Previous studies have revealed that blood pressure achieved during maximal exercise is dependent on underlying heart disease and left ventricle function (2). Some studies have shown that elevated SBP during exercise may indicate a lower probability of severe coronary artery disease and better prognosis in patients with known or suspected CHD (22). The most important findings related to blood pressure response to exercise testing and cardiovascular outcomes are shown in Table I. There was a significant trend toward a lower rate of subsequent mortality in men with higher SBP during the exercise test. Maximal SBP is correlated with the number of obstructed coronary arteries and also with ejection fraction showing the anatomical explanation. This shows that the increased blood pressure response identified among subjects with good left ventricular function could thus generate higher blood pressures with increasing work-loads. It is suggested that the poorer prognosis of persons with lower exercise blood pressures is a consequence of their severe CHD, previous myocardial infarction, and abnormal left ventricular function (2). Systolic blood pressure response to maximal exercise testing adds prognostic information to cardiovascular mortality independent of age, ST segment abnormalities, and exercise capacity. In a recent study a moderate increment in SBP during exercise testing was associated with an improvement in survival (12). However, hypotensive blood pressure response during treadmill exercise tests in patients with known or suspected coronary artery disease has been associated with a higher risk for all-cause and cardiovascular mortality. High-risk subjects with the most extensive cardiac disease may not be capable of generating pressure or work-load to allow the manifestation of exercise systolic hypertension (16).

Table I. Blood pressure response during exercise testing and outcomes.

Study population	Exercise testing protocol	Blood pressure response	Follow-up time	Main finding
1019 elderly men and women, population study (11)	cycle exercise	large SBP increment during exercise	10.6 years	lower risk for cardiovascular death
6216 consecutive men, clinical population (12)	treadmill exercise	large SBP increment during exercise	6.6 years	lower risk for cardiovascular death
9608 consecutive men and women, clinical population (22)	treadmill exercise	high SBP at peak exercise	2 years	lower risk for all-cause death
300 apparently healthy subjects (17)	treadmill exercise	high SBP at peak exercise	7.7 years	higher risk for major cardiovascular events
143 hypertensive men (14)	cycle exercise	high SBP at peak exercise	16 years	higher risk for cardiovascular events
1999 apparently healthy men (20)	cycle exercise	high SBP at moderate work-load	16 years	higher risk for all-cause death
4907 middle-aged men, population study (19)	cycle exercise	high SBP at moderate work-load	8.4 years	higher risk for cardiovascular death
6578 asymptomatic middle-aged men and women (15)	treadmill exercise	high SBP at moderate work-load	20 years	higher risk for cardiovascular death
1731 asymptomatic middle-aged men (13)	cycle exercise	high SBP at peak exercise	12.7 years	higher risk for myocardial infarction

Abnormal resting ECG changes (e.g. Q waves, ST changes) are more common findings among men with the lowest SBP response during exercise (2,6). Previous studies indicate that a poorer prognosis of persons with lower exercise blood pressures is a consequence of their severe CHD, previous myocardial infarction, and abnormal left ventricular function (2). They suggested high specificity of the small SBP changes during exercise for future risk of death and for two- and three-vessel coronary artery stenosis. This indicates that exercise testing with SBP measurements is valuable in defining the persons at the highest risk of death (23).

It is also known that a decrease in blood pressure during exercise is related to the increased risk of CVD. Failure to increase SBP at least 10–30 mmHg, or even a decrease in systolic blood pressure, during exercise has been shown to be an independent predictor of adverse outcome in patients after myocardial infarction (23,24). Furthermore, inability to attain a SBP greater than 110–120 mmHg has been shown to predict poor outcome in patients with previous myocardial infarction (24). Very low increment in SBP reflects inadequate elevation of cardiac output because of left ventricular systolic dysfunction (6,25). An inadequate rise in SBP is not a normal response to exercise.

A poor rise in SBP can result from aortic outflow obstruction, severe left ventricular dysfunction, myocardial ischemia, and certain types of drug therapy (e.g. β-blockers). In most studies, exercise-induced hypotension in association with other measures of ischemia predicts a poor prognosis, with a positive predictive value of 50% for left main or triple-vessel disease (2,26,27). Systolic hypotension during exercise is usually associated with global left ventricular dysfunction (2). Exercise-induced hypotension is also associated with cardiac complications during exercise testing and can occur in subjects with CHD, cardiac arrhythmias, left ventricular track obstruction, valvular heart disease, or cardiomyopathy. Occasionally, subjects without clinically significant CHD will exhibit exercise-induced hypotension during exercise related to dehydration or prolonged strenuous exercise.

Systolic blood pressure recovery from exercise and cardiovascular risk

It has been suggested that abnormal SBP is an important indicator for cardiovascular disease risk not only during exercise but also during the recovery from exercise (28,29). Systolic blood pressure response after the progressive cycle exercise can be considered as a risk predictor for CVD outcomes (5). Our study with blood pressure recordings during cycle exercise test shows that SBP during the recovery period may provide an additional risk marker for identifying asymptomatic individuals at an increased risk for myocardial infarction and stroke (5,29). In the study by Kurl and co-workers, an impaired fall from maximum SBP to recovery markedly increased the risk of stroke (5). Thus, the measurement of SBP immediately after exercise test provides additional valuable information for the risk of stroke.

The rate of the SBP drop during the first minutes of recovery period is usually fairly rapid after maximal exercise. Interestingly, in patients with angina pectoris or coronary artery disease, a high SBP during recovery was related to the diagnosis of multi-vessel coronary artery disease, suggesting the close correlation between this response and the severity of CHD (26). Myocardial ischemia may be one reason for the reduced rate at which SBP level falls (30).

An abnormal decrease of heart rate after exercise is suggested to be due to inadequate reaction of vagal tone because of an increase in activity of the sympathetic nervous system (31); the role of exercise SBP decrease could be similar to heart rate. Consistent with a previous study showing the role of delayed slowing of heart rate (31), elevated SBP immediately after exercise may also reflect the over-activity of the sympathetic nervous system and attenuated vagal reactivation. A population-based study of French civil servants demonstrated that heart rate recovery, a measure of parasympathetic nervous system tone, was predictive of sudden cardiac death (31). During graded exercise, the heart rate and SBP progressively increase, owing to an increase in activity of the sympathetic nervous system with a concomitant decrease in parasympathetic activity. Autonomic dysfunction and vasoreactivity abnormalities may account for the gradual decrease of SBP after exercise (4,16). Finally, an attenuated decrease in exercise blood pressure may also be due to poor arterial compliance in individuals with underlying vascular smooth muscle hypertrophy and subclinical arteriosclerotic changes. An impaired decrease of SBP from peak exercise to rest may indicate high systemic vascular resistance. SBP may remain elevated for a longer time if sympathetic tone does not decrease and vagal tone does not increase during the post-exercise period (32,33).

An attenuated decrease in blood pressure during recovery from exercise may be due to poor arterial compliance in individuals with underlying vascular smooth muscle hypertrophy and subclinical arteriosclerotic changes (23). High blood pressure during recovery from exercise probably also responds with an increase in peripheral resistance. Additionally, it is possible that the steep rise in exercise blood pressure produces poor arterial compliance.

Although part of the mechanisms underlying exercise-related hypertension remain unclear, endothelial dysfunction, inflammation, and elevated arterial stiffness may contribute (34,35). These results suggest that impaired endothelial vasodilatation function may be a mechanism contributing to exercise hypertension and may also be one link between exaggerated exercise blood pressure and worsening hypertension. Additionally, it is also found that that an exaggerated SBP response to exercise is strongly associated with carotid atherosclerosis, independently of conventional risk factors (36). Exercise SBP may be an important factor in evaluating hypertension related to target-organ damage.

Future directions

More information can be derived from exercise capacity, heart rate, and blood pressure responses and the development of arrhythmias during exercise tests as well as heart rate and blood pressure responses and ECG changes during the recovery period. The combined function of cardiorespiratory fitness and hemodynamic data has been related to CVD risk, and it may provide additional valuable information on the evaluation of cardiovascular risk during exercise (37,38). However, further studies are needed the show the role of the combination of cardiorespiratory fitness and blood pressure with respect to CVD risk.

Standardized methods for assessments of blood pressure are necessary for the future evaluation of CVD risk. Clinical exercise testing protocols should avoid a too large increase in work-loads with long duration of exercise (4). We can use exercise blood pressure in addition to resting SBP to select those who may profit by using medication for hypertension, although further studies are needed to show if the use of β-blockers, calcium channel blockers, or other types of antihypertensive medications would be the best choice for exercise hypertensive patients. It is important to understand that the previous observations based on exercise SBP as a risk factor for CVD do not demonstrate any therapeutic value for exercise testing.

It would be valuable for clinicians if we could provide normal exercise blood pressures for those patients who undergo exercise testing. The normal values are well documented in the case of resting blood pressure, and it may be that too low blood pressure as well as very high blood pressure (e.g. over 230 mmHg) are not acceptable findings during exercise. We suggest that SBP values from 160 mmHg up to 200 mmHg, according to exercise testing protocol, and diastolic blood pressure below 90 mmHg are normal findings during exercise testing among subjects without previous CVD. It should be taken into account that normal SBP can be lower among those who have previous CVD. Thus, even more accurate limits of exercise blood pressure would be very helpful for clinicians when they have to make a decision about the treatment strategies on the basis of exercise testing. If other exercise testing findings, including ECG and exercise capacity, indicate effective treatment strategies or further diagnostic tests, the hemodynamic data including blood pressure can be seen as supporting evidence. Exercise testing with the definition of blood pressure can be performed in a logical way with test results used to decide on therapies. It is suggested that emphasis should be shifted from a diagnostic to a prognostic perspective. In recent years, an increasing amount of attention has been directed toward using exercise testing parameters including SBP to measure the therapeutic responses to life-style changes or pharmaceutical and invasive interventions.

Declaration of interest: The paper was supported by a grant from the Finnish Academy. The authors declare no other conflicts of interest.