P. B. M. Clarkson

Impaired Exercise Tolerance in Hypertensive Patients

Sustained arterial hypertension is an asymptomatic condition associated with a major increase in illness and death caused by cardiovascular disease. The development of sustained hypertension in adolescence and adulthood has been defined through studies of blood pressure in children [1]. The prevalence of hypertension increases exponentially from 1% to 2.5% of teenagers [2] to approximately a third of all persons older than the age of 65 years [3]. Blood pressure readings at rest are normally used to define hypertension. During the late 1950s and the 1960s [4, 5], many studies were done to assess the hemodynamic responses to exercise in known hypertensive persons and, separately, in persons who at that time were thought to be at risk for developing hypertension. The results initiated interest in the pathophysiology and natural history of hypertension. It became apparent that functional testing unmasked subtle abnormalities that were not apparent at rest. The recent development of ambulatory blood pressure monitoring has been useful in evaluating blood pressure in an environment that is separate from the stress-filled environment of the physicians office [6]. However, ambulatory blood pressure recordings are not easily correlated with the various physical activities that the patient engages in throughout the day. Standardized exercise testing protocols are now generally available and are an established element of the management of coronary heart disease. These protocols are not routinely used for assessing hypertensive patients unless evidence suggests concurrent myocardial ischemia. In controlled circumstances, formal exercise testing shows that work capacity in asymptomatic hypertensive patients is impaired compared with age- and fitness-matched controls [7]. In this review, we examine the origins and nature of this finding. Despite progress in the understanding of hypertension in terms of diagnosis and assessment of its complications, it is prudent to reexamine the value of exercise testing. Functional testing with modern techniques can give further insights into the pathophysiology of the disorder and may allow a better evaluation of the prognosis of high-risk normotensive persons or those with borderline hypertension. The blood pressure elevation during exercise is better correlated with end-organ damage [8-11] than are casual measurements. Thus, the response to exercise in hypertensive patients may be a more useful end point to assess the efficacy of antihypertensive therapy than is resting blood pressure. In this review we also evaluate the role of exercise testing as an adjunctive investigative tool in hypertension management and drug assessment. Methods We searched the MEDLINE database to identify all articles about exercise testing in persons with hypertension published between 1985 and February 1995. We also searched the bibliographies of relevant textbooks and articles. We analyzed data on hemodynamic responses of hypertensive patients and persons thought to be at risk for developing hypertension in terms of correlations with end-organ damage, death, and exercise tolerance. Where appropriate, we highlight the methodologic flaws of the selected studies to obtain a better understanding of experimental exercise testing. Methodologic Considerations Unlike exercise stress testing in coronary heart disease, no universally accepted guidelines on exercise testing are directed specifically toward assessing hypertensive patients. Few studies have been published on the comparative merits of different exercise-testing protocols. It has even been assumed that otherwise healthy patients with hypertension have normal exercise oxygen kinetics [12]. Most methodologic comparisons have therefore been done on normal persons and on patients with ischemic heart disease or heart failure. Until this vacuum is filled, we must be guided by these research findings. Types of Stress Testing The cardiovascular system can be tested using isometric techniques, isotonic techniques, or both. In clinical practice, hand grip has been used as a beside isometric stress test but is of little use for stressing the whole cardiovascular system. Dynamic or isotonic exercise, which is more often used in research and clinical practice, represents muscle contraction with constant tone and therefore muscle shortening. The cycle ergometer and treadmill are the two commonly used tools. These can be calibrated, and delivered workloads may be accurately defined during staged exercise protocols. The two techniques differ in several respects. Hemodynamic Effects of Body Position Supine cycle ergometry is associated with a higher heart rate for a given level of work than is upright cycle ergometry. Accordingly, with supine ergometry, patients with coronary heart disease develop angina at a lower double product, and the ST segment is more depressed at any given work level [13]. Upright treadmill exercise produces lower peak systolic blood pressure than does supine cycle ergometry at the same workload. When the treadmill and upright cycle ergometry are compared at similar workloads, the increase in both heart rate and arterial blood pressure are lower with treadmill testing [14], but the maximal oxygen uptake is 6% to 25% higher [15-17]. Upright cycle ergometry therefore places a greater stress on the cardiovascular system but is less sensitive in eliciting a positive diagnostic response when the patient is being tested for ischemic heart disease [13]. Exercise Testing Protocols The testing protocol defines the incremental or continuous nature of the test, the duration, and the workload associated with each stage. Measured maximal oxygen uptake differs depending on the protocol used. Maximal oxygen uptake is significantly higher when the test lasts between 8 and 17 minutes [15]. When assessed in patients with heart failure, protocols with slow incremental workloads give reproducible stage indices of metabolic work but result in a longer test and underestimation of maximal oxygen uptake [18]. Protocols that last less than 10 minutes [19] and those with a large incremental increase in workloads [18] are associated with greater variability on repeat testing. The ramp concept was created to minimize this variability. A constant workload rate (ramp rate) is set such that maximal exercise for each person can be achieved in approximately 10 minutes. This protocol provides excellent correlations between observed and predicted oxygen uptake calculated from workloads increased at a constant rate [16]. This is a useful protocol in cases in which ventilatory gas analysis is not available, but it is inconvenient: A preliminary maximal exercise test (using a slow protocol) is necessary to estimate maximal exercise capacity and set the ramp rate. This protocol is therefore not widely used in clinical practice. Whichever protocol is used for research purposes, many studies have shown that patients must be familiarized with the protocol and the demands of the test. The motivation of the supervising staff and patient remain key features in the outcome and duration of a test [20]. Blood Pressure Measurement during Exercise Many studies have shown that at-rest blood pressure measurements obtained using sphygmomanometry may differ from those obtained using intraarterial recordings. In a study of 35 patients with early hypertension, Lund-Johansen [5] found that when an indirect method of cuff sphygmomanometry was used compared with intra-arterial measurements, at-rest systolic blood pressure was underestimated by a mean of 4.5 mm Hg and at-rest diastolic blood pressure was overestimated by a mean of 5.1 mm Hg. His findings are not unique [21, 22]. Gould and colleagues [23] compared indirect and direct blood pressure in 25 patients with hypertension during exercise with cycle ergometry and found that systolic blood pressure during exercise was underestimated by 15 to 18 mm Hg. The mean difference in diastolic blood pressure during exercise ranged from 2 to 4 mm Hg. Diastolic blood pressure is more difficult to determine during exercise. In a separate study of patients with coronary disease [24], diastolic blood pressure could not be measured with a sphygmomanometer during exercise in as many as 12.5% of patients. During exercise, sphygmomanometry is compromised by movement, respiratory effort, and the noise of the equipment. When cuff methods are compared with intra-arterial methods, intrapatient and interpatient variability may increase as exercise progresses [23]. The use of an automated blood pressure measuring system would be more convenient for clinicians supervising an exercise test. Manual and automated methods of exercise blood pressure measurement have also been compared; unfortunately, automated systems tend to be both inaccurate and unreliable [25-28]. Garcia-Gregory and colleagues [25] compared these methods and found that an automated method (the Blood Pressure Measuring System developed by NASA [National Aeronautic and Space Administration]) overestimated systolic blood pressure and underestimated diastolic blood pressure during exercise. At peak exercise, systolic blood pressure was overestimated by 20 mm Hg; in addition, the blood pressure measurements during exercise were inconsistent, with standard errors 2 to 3 times that of the manual method. The utility of Finapres blood pressure estimations (a finger blood-pressure estimation device), which correlate well with intra-arterial monitoring in pressor dose-response studies [29], has not been fully evaluated during exercise. A calculated mean arterial blood pressure (by convention, one third of the pulse pressure plus diastolic blood pressure) is only valid while the patient is at rest. During exercise, measured mean intra-arterial pressure shifts to the middle of the pulse pressure with an increase in heart rate and changing vascular resistance [30]. Because blood pressure during exercise decreases rapidly as

Left atrial size and function: assessment using echocardiographic automatic boundary detection.

OBJECTIVE--To evaluate the waveforms of left atrial area changes obtained by automated boundary detection with newly developed acoustic quantification technology. DESIGN--All subjects had measurements of left atrial areas taken in the apical four chamber, parasternal long axis, and parasternal short axis views using both conventional echocardiographic methods and automatic boundary detection on two occasions separated by at least a week. On the second visit measurements were also repeated in healthy volunteers after acute intravenous volume loading with 1 litre of saline over 2-5 minutes. SETTING--A university medical school echocardiographic laboratory. SUBJECTS--12 healthy male volunteers and 8 patients with cardiac disease (5 with congestive heart failure, 1 with mitral stenosis, and 2 with hypertensive left ventricular hypertrophy, and dilated left atria). RESULTS--There was close correlation between conventionally derived left atrial areas and those obtained by automatic boundary detection, particularly in the apical four chamber view (r = 0.98). Both inter and intra observer variabilities (coefficient of variation) for left atrial areas measured by automatic boundary detection were good (4.7-14.2% and 8.1-18.6% respectively). The reproducibility (coefficient of variation) for derived indices of left atrial function, however, was much poorer (10.4-104.8% and 12.5-88% respectively). After acute volume loading significant increases in left atrial area were observed at all stages in the cardiac cycle. CONCLUSIONS--These data demonstrate that although the reproducibility of left atrial functional indices is poor, instantaneous left atrial cavity measurements with automatic boundary detection are reproducible. This suggests that automatic boundary detection may assist in serial non-invasive measurement of left atrial size to assess disease states and treatments.

Costs Associated with Symptomatic Systolic Heart Failure

AbstractObjective: To investigate whether the extent of systolic dysfunction is a useful predictor of the costs of healthcare and social support for patients with heart failure.n Design: Cross-sectional study with collection of cost data attributed to management of heart failure in the previous year.n Setting: Four primary-care practices in Scotland.n Patients: Patients receiving long term therapy with loop diuretics for suspected heart failure.n Interventions: Two-dimensional and Doppler echocardiography.n Main outcome measures and results: Two hypotheses were tested: (i) the proportion of patients incurring costs is higher in patients with abnormal left ventricular (LV) function; and (ii) the median cost per patient that incurs costs is higher in patients with abnormal LV function.Of the 226 patients in the study, 67 (30%) had abnormal systolic function. In comparison with the remaining 159 patients, they had higher healthcare costs [£560 vs £440 per patient year (1994/1995 values)], were more likely to incur hospital inpatient or outpatient costs [Odds ratio (OR): 2.02; 95% confidence interval (CI): 1.06 to 3.84] and had significantly higher primary-care costs (mean £292 vs £231 per patient year; p = 0.02, Mann Whitney test). In contrast, they were no more likely to incur social support costs (OR: 1.22; 95% CI: 0.52 to 2.86) and the mean cost of social support per patient year was lower (£234 vs £373).n Conclusions: Patients with objectively measured systolic dysfunction incurred significantly higher healthcare costs in the year before diagnosis. This suggests that treatment that improves systolic function will reduce healthcare costs, even in a primary-care population with relatively mild congestive heart failure.n

Systolic and diastolic effects of beta-adrenergic stimulation in normal humans

Abstract We conclude that stimulation of β-adrenergic receptors with low-dose isoprenaline exerts greater effects on myocardial relaxation than contraction. This suggests that diastolic function is exquisitely sensitive to acute changes in sympathetic tone, a finding that may have relevance in the pathogenesis and treatment of disease states associated with impaired ventricular filling.

Profound vagal reactions to brain natriuretic peptide

The haemodynamic and hormonal effects of the structurally similar peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are well documented [3,6]. The precise role of these peptides in man remains controversial and as such, provides the basis for much ongoing research effort. Despite the use of ANP and BNP at high doses and in a wide variety of physiological and pathophysiological states, the incidence of reported side effects has been low. We now report three cases in which profound vagal responses occurred in association with BNP infusion in the setting of high background sympathetic tone.

Left ventricular hypertrophy in hypertension--general and local trends in diagnosis and therapy.

LVH is a frequent echocardiographic finding in the general population but it should be regarded as an ominous predictor of future cardiovascular events rather than an innocent compensatory phenomenon. Echocardiography is the most sensitive and specific method for its detection but the ECG should not be regarded as superfluous since additional prognostic information and information about coexisting myocardial damage is present. The decreasing prevalence of LVH suggests that LVH can be prevented by control of hypertension and prevention of weight gain. Once LVH is present then antihypertensive drugs, weight reduction or salt restriction may promote its reversal, with early studies demonstrating associated improvement in mortality and morbidity.

966-45 QT Dispersion in Essential Hypertension

Increased QT dispersion (QTd) reflects regional variation in ventricular repolarisation, and has been shown in heart failure and hypertrophic cardiomyopathy to relate to an increased incidence of sudden death. As essential hypertensives (EH) are also at increased risk of sudden death we aimed to determine whether increased QTd is found in those EH who are known to be at the highest risk of sudden death. In 50 EH we measured QTd (maximum corrected QT interval minus minimum corrected QT interval), echocardiographic left ventricular mass index (LVMI) (nxa0=xa046 as 4 patients non-echogenic), office systolic and diastolic blood pressure (SSP, DSP), and 24 hour ambulatory systolic and diastolic blood pressure (24 SSP, 24 DSP) (nxa0=xa040). Univariate analysis demonstrated no relationship between QTd and age, sex, height, weight, 24 SSP or 24 DBP. Significant relationships existed between QTd and LVMI (R 2 xa0=xa00.25, Pxa0lxa00.001), SSP (R 2 xa0=xa00.16, Pxa0lxa00.01), DSP (R 2 xa0=xa00.08, Pxa0lxa00.05). Multiple linear regression analysis revealed the only relationships to QTd were LVMI (pxa0lxa00.01) and SSP (pxa0lxa00.05). Excluding 4 patients with electro-cardiographic left ventricular hypertrophy (ECG-LVH) from the analysis a significant relationship between QTd and LVMI (R 2 xa0=xa00.13, Pxa0lxa00.05) and SSP (R 2 xa0=xa00.10, Pxa0lxa00.05) persists. These demonstrate that increased QTd is found in EH with the highest risk of sudden death (greatest SSP and LVMI). This relationship persists in the absence of ECG-LVH. Further study of QTd, as a predictor of sudden death in EH is warranted.