Q J Med 2000; 93: 703-705
© 2000 Association of Physicians
Editorial |
Step test in hypertension
Department of Cardiology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4KN
The physiological basis of essential hypertension is a continuing rise in the systemic vascular resistance (SVR) over time, a process which does not appear to be halted by drug treatment that normalizes diastolic blood pressure (BP).1 Since SVR is a major determinant of BP in the absence of left ventricular (LV) systolic dysfunction, BP rises in parallel with the SVR. This can easily be demonstrated with drugs such as phenylnephrine or cyclosporin that increase the SVR. It was previously thought that peripheral vasoconstriction was a ‘protective’ response to an early hyperkinetic circulation. However, this hypothesis has largely been discounted.2 Hypertension is thus the response to an increased SVR, the aetiology of which is still unclear. The increased pressure generated within the left ventricle to maintain a high level of systemic arterial BP has an inherent tendency to cause cardiac dilatation. To prevent this from happening, the natural adaptive response is to dissipate the excess pressure through LV wall thickening. We now know that reversing hypertensive LV hypertrophy (LVH) with treatment may improve prognosis.3 However, resting BP, the measure currently used to manage hypertension, is not a good predictor of LVH. Perhaps this partly explains why control of resting BP does not normalize cardiac mortality4 or stroke risk.5 Furthermore, it has been noted that in some patients with apparently well-controlled resting BP, LVH may persist6 or even continue to increase.7
The Laplace equation states that LV wall thickness directly relates to BP via LV wall stress. In isolated systolic hypertension, diastolic BP becomes a negative risk factor and the systolic-diastolic difference or pulse pressure offers additional prognostic information.8 This suggests that rapidly fluctuating extremes of BP, which can be accentuated by physical activity, may be harmful.9 Because the maximum LV wall stress occurs during systole, the systolic BP is a more powerful determinant of LVH than the diastolic BP. This finding is consistent regardless of the method used to measure BP, whether in the clinic, during exercise or over 24 h with ambulatory techniques.10 In turn, the submaximal exercise systolic BP (ExSBP) at a workload of 4.7–7.1 metabolic equivalents (1 MET=3.5 ml/kg/min, basal oxygen consumption) is a better predictor of LVH than clinic or ambulatory BP measures.11 The prognostic value of ExSBP over that of resting BP has been established. Filipovsky et al.12 reported that a high ExSBP at 5 min during cycle ergometer (progressing from 82W for 2 min to 164W for 6 min, 
5–9 METs) was an independent predictor of cardiac mortality (relative risk of 1.6, ExSBP 
230 mmHg vs. <230 mmHg) in a population-based study involving 4907 middle-aged men with an entry BP 
180/105 mmHg, followed-up over a mean period of 17 years. In a separate study, Mundal et al.,13 using a 6-min 100W (6–7.5 METs) protocol on 1999 middle-aged men, reported that amongst participants with a resting systolic BP 140 mmHg, those with an ExSBP 200 mmHg had a mortality rate of 16.1% (vs. 6%, ExSBP <200 mmHg) over a mean follow-up period of 16 years.
With the above in mind, and the lack of a simple technique to measure ExSBP in hypertension, we developed the Dundee step test to facilitate further research in this area.14 This is a simple protocol that uses a 17.5 cm step and a stepping rate of 92 set using a metronome. The ExSBP obtained immediately following 3 min of exercise can be reproducibly measured. This ExSBP correlates well with that obtained during bicycle ergometry at the same workload of about 5 METs.14 The low exercise intensity of this step test is similar to that used in large outcome trials and mimics the activities of daily living which to a large extent account for BP variability.9 The exercise test can be completed by most subjects irrespective of cardiovascular fitness. Hence, the Dundee step test can practically be implemented into an ambulatory clinic setting.
In a recent study from our centre, the ExSBP obtained using the Dundee step test was a better measure than resting BP in deciding whether sustained hypertension was present.15 Using a definition of mean daytime ambulatory BP 140/90 mmHg as indicative of sustained hypertension, the positive predictive value of a resting diastolic BP 90 mmHg and resting systolic BP 140 mmHg for sustained hypertension were 64% and 67%, respectively in 191 consecutive hypertension clinic referrals. In comparison, an ExSBP 180 mmHg had a positive predictive value of 76%, and this rose to 93% if an ExSBP 210 mmHg threshold was used. Another study examined clinic BP control and ExSBP. Of 41 hypertensives (taking a mean of two antihypertensive agents) who had ‘controlled’ BP (mean 137/ 85 mmHg), 34% had an ExSBP 180 mmHg.16 It seems probable that such treated hypertensives with an uncontrolled ExSBP are at higher risk of cardiovascular disease or premature death. In order to determine whether or not this is the case, a step test sub-study of the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) is being carried out.17
Aside from LVH, ExSBP is also an independent predictor of another important prognostic marker, the maximum heart-rate-corrected QT interval (QTcmax).18 This relationship was uncovered in a relatively small study involving only 29 untreated hypertensives free from ischaemic heart disease with a mean age of 51 years. Five subjects (17.2%) had prolonged QTcmax 430 ms, a risk factor for sudden cardiac death.19 These subjects were not differentiated by 24-h ambulatory BP [146/83 vs. 140/88 mmHg, p=NS] but were differentiated by ExSBP [226 vs. 188 mmHg, p=0.002].
Previous commentators have suggested that ExSBP adds little information to that obtained from measuring resting BP.20 One key question is whether an exaggerated rise in ExSBP is of any clinical significance. Physiologically, the ExSBP rise is an indirect measure of the peripheral vasodilatory capacity. In normal subjects, the SVR falls during exercise as a result of peripheral vasodilatation which blunts the rise in ExSBP. ‘Abnormal’ subjects and hypertensives, however, have reduced peripheral vasodilatory capacity predisposing to an uncontrolled rise in ExSBP.1 This failure of vasodilatation might be related to vascular endothelial dysfunction, since it is well-documented that subjects with diabetes and hypercholesterolaemia have endothelial dysfunction that predisposes to high ExSBP.21 We have preliminary unpublished data that indicate an abnormal rise in ExSBP predicts vascular endothelial dysfunction in hypertensive patients.22 Such hypertensives may also have worse LV diastolic function, limiting exercise tolerance.23 Interestingly, angiotensin receptor antagonists partially reverse these abnormalities.24 This fits in with the theory that drugs which improve vascular endothelial function may limit the rise in ExSBP.
Aldosterone might be a possible aetiological factor responsible for the increased SVR in hypertension. Indeed, non-suppression of plasma aldosterone in response to salt loading can be demonstrated in at least 1 in 10 hypertensive subjects suggesting hyperaldosteronism,25 but a varying degree of ‘aldosteronism’ is likely to be present within the wider hypertensive population. Komiya et al.26 used the aldosterone to renin ratio (ARR) as a marker of inappropriate aldosterone activity and found significant positive relationships between this index with age and plasma sodium concentration in 741 hypertensives. We found that ExSBP significantly and independently correlated with the ARR (r=0.24, p<0.001) in a cross-sectional study involving 119 untreated hypertensive subjects.27
The Dundee step test allows ExSBP to be easily measured, and this will facilitate future studies of possible treatment for high ExSBP. To reduce ExSBP, a treatment must either lower the baseline BP or limit the rise in BP during exercise.23 From the studies published so far, there can be little doubt that a high ExSBP is a risk factor for cardiovascular disease. The risk is likely to rise continuously (but not necessarily linearly) with the magnitude of ExSBP. The precise values at which the risk becomes importantly different from clinic BP remains to be determined, however, subjects at the upper extremes of the general population are likely to be at increased risk. Thus the Dundee step test seems a reasonable and simple tool for identifying such subjects, even those who are currently normotensive at rest. The place of the Dundee step test in managing risk must await further work. However the restoration of ‘normal’ peripheral vasodilatation on exercise, which is likely to mean the reversal of abnormal endothelial function, seems a laudable goal. Perhaps we should preferentially use non-pharmacological (diet28 and exercise29) and pharmacological30 treatments that improve the endothelial function.
References
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