Individual differences in susceptibility to psychologic factors
The effects that a given level of perceived stress will have on the cardiovascular system will depend to some extent on the physiologic susceptibility of the individual. In other words, for a given intensity of a stressor, some individuals will be more reactive than others. In practice, it may be difficult to separate the physiologic and psychologic components of reactivity, but conceptually this distinction is important. Of all the components of the potential interactions between stress and blood pressure, reactivity has received much more attention than any other, and perhaps more than it deserves.
Reactivity Hypothesis
In its simplest form, the reactivity hypothesis states that individuals who show increased cardiovascular reactivity to psychologically stressful stimuli are at increased risk of developing cardiovascular disease. The latter is often taken to include hypertension and coronary heart disease as if they were a single entity, which of course they are not. Two forms of the hypothesis as it relates to hypertension have been proposed: in one, the “Recurrent Activation Model,” the response to laboratory tests, is assumed to be correlated with intermittent pressor responses to stress occurring in everyday life, whereas in the other, the “Prevailing State Model,” the laboratory response predicts the average level of blood pressure. It has also been suggested that stressors initially produce transient elevations in blood pressure by neurohormonal mechanisms, and that these elevations may in turn induce structural changes in the arterial wall, which eventually results in a sustained increase in vascular resistance and hence blood pressure. This mechanism is usually thought to be elicited by stimuli that are psychologically stressful, but there is no clear reason why it should not also apply to physically stressful stimuli such as exercise.
It must be admitted, however, that direct evidence in support of this mechanism is limited. It has recently been demonstrated, e.g., that neurogenically produced pressor episodes do not on their own lead to any sustained increase in the basal blood pressure level, although they can produce left ventricular hypertrophy. And exercise training, which certainly produces intermittent neurogenically mediated pressor episodes, results in a reduction in the resting blood pressure level.
Some of the criteria that this hypothesis must satisfy have been reviewed elsewhere. First, the degree of reactivity for an individual subject should be stable over time; second, it should, to some extent, be generalizable from one type of challenge to another; third, it should be generalizable from the laboratory to the stresses of everyday life; and fourth, reactivity should be an independent predictor of disease.
The test-retest reliability of blood pressure changes measured during reactivity testing is not very good, with correlation coefficients ranging from about 0.4 to 0.7. Surprisingly, few studies have systematically examined the extent to which an individual subject’s response to one task will predict his or her response to another. Parati et al. found that the responses to two predominantly mental tasks (mental arithmetic and mirror drawing) were quite well correlated with each other (r = 0.78, k 0.01), and also the response to two predominantly physical tasks (isometric exercise and the cold pressor test), but correlations between the responses to the mental and physical tasks were not significant. Fredrikson et al. examined the correlation between the change scores for four tasks: an attentional demands task, mental arithmetic, the cold pressor test, and isometric exercise. The only significant correlation for systolic pressure was between mental arithmetic and isometric exercise in normotensive subjects; for hypertensive subjects none of the correlations was significant. By contrast, Turner et al. found significant correlations between four tasks (two involving speech and two mental arithmetic) ranging from 0.62 to 0.80 for systolic pressure, and considerably lower for diastolic. These results suggest that there is limited evidence for generalizability of reactivity across dissimilar tasks, and that characterizing an individual as being generally “hyper-reactive” has little validity at the present time.
Physiologic and Demographic Factors Affecting Reactivity
Several studies have compared blood pressure reactivity in normotensive and hypertensive subjects. We reviewed a selection of these that gave adequate details of the actual blood pressure levels and stastistical comparison. The two most extensively studied tests have been mental arithmetic and the cold pressor test. We concluded that there is a tendency for hypertensive subjects to show increased reactivity to behavioral, but not physical tasks. A more formal meta-analysis was undertaken by Fredrikson and Matthews. They concluded that patients with essential hypertension (with blood pressures of at least 165/95 mmHg) showed an exaggerated systolic blood pressure response to passive stressors (including the cold pressor test), in comparison to normotensive controls, although this was seen in only 31 of 63 studies. Overall, borderline hypertensive subjects showed a significantly greater response to active stressors (in 8 of 25 individual studies).
The only population-based study, conducted in 169 men and 120 women by Julius et al. in Tecumseh, Michigan, did not find any correlation between reactivity to mental arithmetic or isometric exercise and the resting level of blood pressure. They pointed out that one reason for the discrepancy between their findings and those of other studies comparing normotensive and hypertensive subjects was that their subjects were not necessarily aware of which diagnostic group they were in, whereas in most other studies they were. The importance of this is that it has been shown by Rostrup and Ekeberg that labeling subjects as hypertensive increases their blood pressure reactivity.
Several studies have examined the influence of family history of hypertension on reactivity, and many have dealt with children. The meta-analysis by Fredrikson and Matthews concluded that 13 of 30 studies demonstrated an increased blood pressure or heart rate reactivity in association with a positive family history, and that overall this effect was significant in comparison with subjects without a family history. The difference was more reliable for active than passive tasks. However, one study reported that the blood pressure response to dynamic exercise was exaggerated in subjects with a family history of hypertension in comparison to those without one. A more recent study of normotensive young adults found that subjects with a positive family history (either one or both parents hypertensive) had higher baseline blood pressures (measured both in the laboratory and during ambulatory monitoring) but did not show an exaggerated blood pressure response to four different stressors. The Tecumseh study did not find any association between blood pressure reactivity and family history.
Psychologic Factors Influencing Differences in Reactivity
As already reviewed, attempts to relate a specific personality type with hypertension have been, on the whole, disappointing. The picture is a little better with blood pressure reactivity: in a meta-analysis of 71 studies comparing cardiovascular reactivity in type A and type В individuals, Harbin concluded that type A men showed a consistently greater reactivity of systolic (but not diastolic) pressure and heart rate to cognitive challenges. In parallel with these findings, it has also been reported that men and women scoring high on tests of hostility have a larger blood pressure reactivity when attempting a frustrating task.
With mental challenge tasks requiring an active response by the subject, it is to be expected that the subject’s attitude to the task will affect the response. This has been confirmed in a study by Smith et al., who found that the increase in blood pressure occurring during talking is much greater if the person who is talking is trying to persuade another person to change his or her opinion about something, compared to just talking alone.
Does Reactivity Measured in the Laboratory Predict blood pressure Changes During Everyday Life?
The rationale generally proposed for the use of laboratory tests of cardiovascular reactivity is that an individual’s response to such a test may predict how he or she will respond to stressful situations in real life. Until quite recently, it has not been possible to test this assumption, but with the introduction of ambulatory monitoring techniques it can now be attempted.
Four studies have compared the response to laboratory stressors with blood pressure variability measured with the intra-arterial technique of ambulatory monitoring. Several studies have used noninvasive ambulatory monitoring techniques. Because blood pressure is recorded intermittently rather than continuously by this technique, the characterization of blood pressure variability and reactivity is inevitably less precise than with intra-arterial monitoring. All these studies found very low or absent correlations between blood pressure reactivity (measured as change scores) and ambulatory blood pressure.
Viewed as a whole, these studies suggest that if there is an association between reactivity measured in the laboratory and the blood pressure variability or reactivity of daily life, it is rather weak, or is obscured by the problems of measurement error. Furthermore, it appears to be quite nonspecific; that is, it can be demonstrated equally well (or poorly) with laboratory challenges both with and without a strong behavioral component. The simplest explanation of the few positive findings is that there are significant interindividual differences in blood pressure variability that may be detected both by laboratory testing and by ambulatory monitoring. As they stand, the results of these studies provide little evidence that the type of reactivity testing commonly used in the laboratory is an ecologically valid representation of the stresses of everyday life. Yet, the assumption of such validity is the basis for much of the work being done in this field. It seems clear that a great deal of research must be done in this area before conclusions can be drawn.
In the Tecumseh population study of 169 men and 120 women, two indices of reactivity (mental arithmetic and isometric exercise) were related to two measures of target organ damage (left ventricular mass and minimal forearm vascular resistance). Subjects classified as hyperreactors to mental arithmetic did not show any greater signs of vascular damage than the others.
Prognostic Significance of blood pressure Reactivity
Blood pressure is not the only factor that can be used to predict hypertension. A family history of hypertension is also of major importance. In Thomas ‘s prospective precursors study of medical students at Johns Hopkins University, it was found that subjects who had two hypertensive parents and a high initial clinical systolic pressure (above 125 mmHg) were 12.6 times as likely to become hypertensive over a 30-yr follow-up period as subjects without these risk factors. The study also found that reactivity to the cold pressor test failed to predict future hypertension, but a subsequent analysis, published in 1989, and using more sophisticated statistical techniques, found that after adjusting for age, obesity, baseline blood pressure, and smoking, an exaggerated response to the cold pressor test did predict the development of hypertension after an interval of 20 yr. Without these adjustments there was still no association, however. Other prospective studies have reported mixed results, mostly negative.
Two studies have reported that the reactivity to mental arithmetic, which has more of a psychologic component than the cold pressor test, does predict future blood pressure. The first, by Falkner et al., followed 80 adolescents with borderline hypertension for up to 5 yr. The development of hypertension was predicted both by a positive family history and by an exaggerated blood pressure response to mental arithmetic. The relative importance of the two was not evaluated. The second study, by Borghi et al., reported that subjects with a positive family history and borderline hypertension showed an increased reactivity to both behavioral and physical challenges, and that they were more likely to become hypertensive over a 5-yr period. Overall, the evidence that blood pressure reactivity is an independent predictor of future blood pressure status is unconvincing.
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