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Blood Pressure Reactions to Stress and the Prediction of Future Blood Pressure: Effects of Sex, Age, and Socioeconomic Position

From School of Sport and Exercise Sciences (D.C., C.R.) University of Birmingham, Birmingham, England and MRC Social and Public Health Sciences Unit (K.H., G.F., S.M.), University of Glasgow, Glasgow, Scotland.

Address correspondence to Douglas Carroll, PhD, School of Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT, England. E-mail carrolld{at}bham.ac.uk

	ABSTRACT

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OBJECTIVE: This epidemiological study examined whether the magnitude of blood pressure reactions to mental stress was associated with future blood pressure and whether the strength of association was affected by sex, age, and socioeconomic position.

MATERIALS AND METHODS: Resting blood pressure was recorded at initial baseline and in response to mental stress. Five-year follow-up resting blood pressure data were available for 990 (68%) of the participants; 333 were 23 years old at the time of stress testing, 427 were 43, and 230 were 63. There were 541 women and 449 men; 440 came from manual and 550 from nonmanual occupation households.

RESULTS: Systolic blood pressure reactions to stress correlated positively with follow-up systolic blood pressure; no association was found for diastolic blood pressure reactions and follow-up diastolic blood pressure. In multivariate tests, systolic reactivity remained predictive of follow-up systolic blood pressure and accounted for 2.3% of the variance not explained by age, body mass index, and initial baseline systolic blood pressure. Systolic and diastolic reactivity predicted 5-year upward drift in systolic and diastolic blood pressure respectively, accounting for an additional 3.6% and 2.9% of variance, respectively, in multivariate models. The predictive value of reactivity was greater for participants from manual occupation households and tended to be greater for men.

CONCLUSIONS: The results of this study indicate that blood reactions to mental stress predict future blood pressure status and the increase in resting blood pressure over time. The magnitude of the prediction appears to vary with socioeconomic position and sex.

Key Words: blood pressure, • reactivity, • age, • sex, • socioeconomic position, • prospective study.

Abbreviations: BMI = body mass index;; BP = blood pressure;; DBP = diastolic blood pressure;; PASAT = paced auditory serial addition test;; SBP = systolic blood pressure.

	INTRODUCTION

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Heightened blood pressure (BP) reactions to acute psychological stress have been implicated in the development of cardiovascular disease (1–3). Although consideration has been given to the association between BP reactions to stress and clinical outcomes such as carotid atherosclerosis (4), carotid intima-media thickness (5,6), and left ventricular mass (7,8), future BP status has remained the most popular focus (9). Unfortunately, the results of prospective studies of BP reaction to stress and future BP levels have been somewhat inconsistent. While several studies present evidence that the magnitude of the BP reactions to the cold pressor test predicts future BP status independently of resting BP at entry to the study (10–13), a similar number have found either minimal or no independent association (14–18). It can be argued, though, that the cold pressor provides a poor test of the hypothesis linking reactivity and pathology (3). First, the reactivity hypothesis, as originally conceived and propagated (1,2), focused on reactions to active mental stress tasks rather than passive physical stress tasks. Second, the cold pressor test would seem to be a poor analogue of everyday stress (19).

The results of studies using mental stress exposures, which involved active behavioral engagement or coping, are somewhat more compelling. Earlier studies, however, were limited by either small and highly selected samples (20–22) or failure to control for resting BP at entry (21,22). In a study of 246 children, systolic blood pressure (SBP) and diastolic blood pressure (DBP) reactions to a video game were found to add significantly to the prediction, offered by resting BP at entry, of SBP and DBP levels 5 years later; unfortunately, the effect size cannot be discerned (23). No such difficulty attends the report of a 3- to 4-year follow-up of 83 adolescents (24). In this case, however, the bivariate association between SBP reactivity to a video game and follow-up SBP was not statistically significant. Nevertheless, SBP reactivity emerged as a predictor in multivariate analysis and accounted for 4% of the variance in follow-up SBP not explained by age, body mass index, and baseline SBP. In a study of 152 children and 168 middle-age adults, BP reactions were measured to a range of laboratory stress tasks and were observed to predict BP levels 6.5 years later, independently of resting BP at entry (25). For the adult sample, magnitude of BP reaction accounted for an additional 1% to 6% of the variance in prospective BP, depending on the stress task. Effects of a similar order emerged for the child sample. Using established hypertension as the 4-year outcome, BP reactions to the anticipation of exercise in 508 adult men were found to predict subsequent hypertension in logistic regression models that adjusted for age and resting BP level (26). SBP reactivity conferred an increased risk of 3% and DBP reactivity an increased risk of 7%. In the CARDIA study of more than 3000 adult men and women, SBP reactions to a video game were independently associated with an increased risk of upward drift in BP over 5-year follow-up (27). Finally, in reports of the 5-year follow-up of 1003 and the 10-year follow-up of 796 United Kingdom public servants, SBP, but not DBP, reactions to a mental stress task predicted follow-up BP. In multivariate models that included age and measures of initial resting SBP, however, SBP reactivity accounted for only 1% of the variance in follow-up SBP (28,29). In sum, the available data point to a reasonably consistent but, on occasion, very modest association between BP reactions to stress and future BP status.

Many of the larger prospective studies only tested men (26,28,29). An exception here is the CARDIA study (27). The association between SBP reactivity and upward blood pressure drift over 5-year follow-up held for men but not women. The issue of sex differences merits further investigation. Further, examination of age differences is also warranted. While relationships between BP reactivity and future BP have been observed for various age groups, a recent review concluded that associations were more compelling in younger samples (9). In addition, the largest study to date of reactions to the cold pressor test, found that associations between magnitude of reaction and hypertension held only for those younger than 45 (12). There are also theoretical reasons for expecting stronger associations in younger cohorts. Because high-magnitude reactions to stress are presumed to lead to upward resetting of BP across the life course, the opportunity for such effects to have occurred will be less in younger individuals, and accordingly resting BP and BP reactivity will be less confounded. Finally, using carotid intima-media thickness as the outcome, an interaction between BP reactivity and socioeconomic position was recently reported (6); men with higher SBP reactions to exercise anticipation and who were of low socioeconomic position showed greater deleterious changes in carotid artery characteristics across 4-year follow-up. Although the conclusions drawn from this study have been challenged (30), the data nevertheless suggest that the implications of excessive BP reactivity may vary with socioeconomic position. The present study, then, revisited the prognostic significance of BP reactions to mental stress in a large sample that comprised three age cohorts, included both men and women, and embraced participants from both manual and nonmanual occupation households.

	MATERIALS AND METHODS

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Subjects
Data were collected as part of the West of Scotland Twenty-07 Study (31). Participants were from the Glasgow area and were excluded if they reported using antihypertensive medication or registered resting SBP 160 mm Hg or more and DBP 90 mm Hg or more. These exclusions left a sample of 1458, made up of 558 23-year-olds, 565 43-year-olds, and 335 63-year-olds, of whom 792 were women and 666 men, and 650 were from manual and 808 nonmanual occupation households who all underwent stress testing. Five years later, 990 (68%) were successfully re-assessed; their average age when they undertook the stress test was 41.7 (SD = 14.81) years and their average body mass index (BMI) at that time was 25.6 (standard deviation [SD] = 4.23) kg/m². This sample of 990 comprised: 333 (60%) of the youngest cohort (mean age 23.7, SD = 0.54 y), 427 (76%) of the middle cohort (mean age = 44.0, SD = 0.80 y), and 230 (69%) of the oldest cohort (mean age = 63.1, SD = 0.74 y); 541 (68%) women (mean age = 41.8, SD = 14.97 y) and 449 (67%) men (mean age = 41.5, SD = 14.64 y); 440 (68%) individuals from manual (mean age = 41.8, SD = 14.81 y) and 550 (68%) from nonmanual households (mean age = 41.5, SD = 14.83 y).

Apparatus and Procedure
Testing sessions were conducted by trained nurses in a quiet room in the participants’ homes. Demographic information and medication status were obtained by questionnaire. Household socioeconomic position was characterized as manual and nonmanual from the occupational status of the head of household, using the Registrar General’s classification system of occupations (32). For the older two cohorts, head of household was the person, self or spouse, with the higher occupational status, whereas for the youngest age cohort, head of household was the parent with the higher occupational status. Height and weight were measured and BMI was computed. The stress task was the paced auditory serial addition test (PASAT), which has been shown to reliably provoke BP increases (33). Participants were presented with a series of single digit numbers by audio tape and requested to add sequential number pairs while retaining the second of the pair in memory for addition to the next number presented and so on throughout the series. Answers were given orally and, if participants faltered, they were instructed to recommence with the next number pair. The correctness of answers was recorded as a measure of performance. The first sequence of 30 numbers was presented at a rate of one every 4 seconds, and the second sequence of 30 at one every 2 seconds. The whole task took 3 minutes, 2 minutes for the slower and 1 minute for the faster sequences.

BP was determined by an Omron (model 705CP) semi-automatic sphygmomanometer, a device recommended by the European Society of Hypertension (34). After questionnaire completion (approximately 1 hour), there was then a formal 5-minute period of relaxed sitting, at the end of which a resting baseline reading was taken. Task instructions were then given and the participant allowed a brief practice to ensure that they understood the requirements of the PASAT. Two further BP readings were taken during the task, the first initiated 20 seconds into the task (during the slower sequence of numbers), and the second initiated 110 seconds later (at the same point within during the faster sequence). For all BP readings the nurses ensured that the participant’s elbow and forearm rested comfortably on a table at heart level. The two task readings were averaged, and the resting baseline value subtracted from this average to yield reactivity measures for SBP and DBP. Follow-up BP was determined using the Omron in the participants’ homes, on average 5.1 (SD = 0.51) years later. After a 5-minute period of relaxed sitting, two readings were taken, approximately 1 minute apart, and averaged to yield follow-up values for SBP and DBP. The method of measuring BP was identical to that used 5 years previously.

Statistical Analyses
ANOVA was used to determine whether increases in SBP and DBP to the PASAT were statistically significant, as well as to compare initial resting baseline and follow-up SBP and DBP to analyze the upward drift in BP levels during the intervening follow-up. ANOVA and ANCOVA were used to assess demographic differences in both reactivity and upward drift in BP. eta² is reported as a measure of effect size. Analysis of possible predictors of follow-up SBP and DBP was by correlation and multiple linear regression. Initial focus for regression analyses was the whole sample, after which analogous models were tested separately for women and men, the three age cohorts, and individuals from manual and nonmanual, as determined at the time of stress testing, occupation households. Following-up from another large population study (27), similar correlation and regression analyses were applied with BP upward drift (follow-up BP minus initial resting baseline BP) as the outcome.

	RESULTS

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Blood Pressure Reactions to Mental Arithmetic Stress
Table 1 presents the means and SD for the key BP variables. The increases in SBP and DBP to the mental stress task were statistically significant, (F = 1077.81, p < 0.001, eta² = 0.522 and F = 665.92, p < 0.001, eta² = 0.402, respectively). The magnitude of SBP reactions did not vary between participants from manual and nonmanual households (F = 0.00, p = 0.98, eta² = 0.000), but did differ between sexes (F = 4.14, p = 0.04, eta² = 0.004); the mean increase in SBP reactivity for men was 13.05 (SD = 12.11) and for women was 11.53 (SD = 11.53) mm Hg. This effect, however, was attenuated after adjustment, in ANCOVA, for variations in performance on the PASAT (F = 2.90, p = 0.09, eta² = 0.003). In addition, SBP reactivity varied with age cohort (F = 5.73, p = 0.003, eta² = 0.011), an effect that was, if anything, strengthened after adjustment for performance (F = 7.59, p < 0.001, eta² = 0.015). The mean unadjusted increases in SBP for the youngest, middle, and oldest cohorts were 10.52 (SD = 10.39), 12.81 (SD = 11.48), and 13.60 (SD = 13.53) mm Hg, respectively; post hoc analyses, using the Newman-Keuls method, revealed that the youngest cohort were significantly less reactive than the other two cohorts. There was no difference in DBP reactivity between sexes (F = 1.40, p = 0.24, eta² = 0.007), socioeconomic groups (F = 0.42, p = 0.52, eta² = 0.000), nor among the three age cohorts (F = 0.04, p = 0.96, eta² = 0.000).

Finally, those who remained in the study showed larger SBP and DBP reactions to mental stress than those who were lost to follow-up; the difference for SBP reactivity was 1.78 mm Hg (F = 7.44, p = 0.006, eta² = 0.005), and for DBP reactivity was 1.07 mm Hg, (F = 4.87, p = 0.03, eta² = 0.003). This could have reflected relatively greater loss to follow-up of participants from the youngest and more geographically mobile age cohort (² = 32.70, p < 0.001), who, as reported, showed smaller reactions, at least for SBP.

Predictors of BP at 5-Year Follow-up
Table 2 presents the results of bivariate correlational analyses applied to the whole sample. Because the magnitude of DBP reactions to mental stress was not associated with follow-up DBP, multivariate analyses focused on the significant univariate predictors, including SBP reactivity, of follow-up SBP. The following variables were examined as potential independent predictors of follow-up SBP, using stepwise multiple regression: age at entry, BMI at entry, initial baseline SBP, and SBP reactions to mental stress. As can be seen in Table 3, all four variables entered the equation, and the overall model accounted for 50% of the variance in follow-up SBP. While initial resting SBP afforded the strongest prediction of follow-up SBP, accounting for 43% of the variance, there was an additional contribution from SBP reactivity that accounted for a further 2.3%.

Predictors of 5-Year Upward Drift in BP
Bivariate correlational analyses applied to the whole sample indicated that the magnitude of SBP reactions to mental stress was positively associated with the upward drift in SBP across the 5 years of follow-up (r = 0.28, p < 0.001). DBP reactivity was similarly associated with follow-up DBP (r = 0.31, p < 0.001). Thus, multivariate regression analyses were applied to both SBP and DBP drift. The following variables were examined as potential independent predictors of upward drift in SBP using stepwise multiple regression: age, BMI, initial baseline SBP, and SBP reactions to mental stress. Parallel analyses were conducted using upward drift in DBP as the dependent variable: age, BMI, initial baseline DBP, and DBP reactions to mental stress were tested. The outcomes of these two analyses are summarized in Table 7. In each case, all four variables entered the equations, and the overall model accounted for 22% of the variance SBP drift and 30% in the case of DBP drift. Initial resting SBP afforded the strongest independent prediction of upward drift in SBP and with age accounted for 18% of the variance; however, there was an additional contribution from SBP reactivity that accounted for a further 3.6% of the variance. Initial resting DBP was again the strongest predictor of upward drift in DBP, accounting for 25% of the variance. DBP reactivity entered the equation next, accounting for a further 2.9% of the variance.

	DISCUSSION

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There was a significant bivariate association between the SBP reactions to mental arithmetic stress and 5-year follow-up SBP and, in multivariate analyses, SBP reactivity accounted for 2.3% of the variance in follow-up SBP additional to that explained by age, BMI, and initial baseline SBP. No analogous bivariate relationship was observed between DBP reactivity and follow-up DBP. The size of the association between SBP reactivity and follow-up SBP in the present study is larger than the approximate 1% additional contribution to follow-up SBP variance found in other prospective studies in the United Kingdom (28,29) and is larger or of the same order as that reported in studies in the United States (25,27). One difference between this and earlier United Kingdom reports is that the latter included a clinical baseline BP assessment, using a Hawksley random zero sphygmomanometer, in addition to the baseline, taken with a semi-automatic device, before the stress. The reason for the inclusion of the clinical baseline in these earlier reports was that follow-up SBP was also measured by the Hawksley. In the present study, follow-up BP was assessed using the same device used to measure reactivity. Nevertheless, before stress testing, one resting BP reading was taken using the Hawksley in the present study and its inclusion in multiple regression models changed nothing. Overall, the magnitude of SBP reactions to mental stress still accounted for the exact same 2.3% of the variance in follow-up SBP. Considering prospective studies of BP reactions to mental stress as a whole, it is reasonable to conclude that SBP reactivity does add to the prediction of future SBP. It remains unclear, however, what the practical clinical significance of effects of the size found might be, given that initial resting BP remains a considerably stronger predictor of follow-up BP. At the same time, though, the present data, in the context of other positive results, add force to the general theoretical position that heightened cardiovascular reactions to stress can contribute to the development of cardiovascular disease (9).

SBP reactivity proved to be a stronger predictor of upward drift in SBP than of follow-up SBP per se, accounting for 3.6% of the variance not explained by other predictor variables. Moreover, DBP reactions to mental stress correlated significantly with the outcome measure, ie, upward drift of DBP, and explained an additional 2.9% of the variance in DBP drift in multivariate analysis. It is worth noting that there was a negative relationship between initial baseline BP and drift in BP during follow-up (Table 7), which could reflect regression to the mean or a greater likelihood that those with relatively high BPs at baseline would be receiving antihypertensive medication by follow-up, and as a consequence register small upward drifts in BP. In any case, the present results indicate that excessive BP reactions to mental stress are associated with the extent of upward resetting of basal BP and, as such, could possibly be a factor in the development of essential hypertension (1–3).

In contrast to the results of the CARDIA study (27), the association between reactivity and subsequent BP status held for both men and women, although reactivity tended to be a stronger predictor for men. This was the case irrespective of whether follow-up BP or upward drift in BP served as the outcome. One reason why the present results may be more compelling for both sexes than those reported from CARDIA is the extent of the upward drift in BP during the 5-year follow-up, which was just more than 1 mm Hg for both SBP and DBP in the CARDIA study but 6 mm Hg and 3 mm Hg for SBP and DBP, respectively, in the present study. It is also worth noting that the other study to examine sex differences in this context found no difference in the predictive value of reactivity for male and female participants (25).

It has been concluded recently that particularly consistent and robust associations between reactivity and future BP status emerge from studies of younger samples (9) and a preponderance of older participants in some prospective studies might be a reason for the modest associations reported (28,29). The present study is uniquely placed to consider age variations in the predictive power of reactivity. With follow-up SBP per se as the outcome, there is some evidence from the present analyses in favor of the proposition that reactivity is more predictive in younger cohorts. This is especially evident when the ratios of the independent contributions of SBP reactivity and initial baseline SBP to follow-up SBP (defined as R² for reactivity/R² for initial baseline) for the three cohorts are considered; these were 0.12, 0.09, and 0.07 for the youngest, middle, and oldest cohorts, respectively. A slightly different pattern of results, however, emerged with upward drift in SBP as the outcome measure. In this case it was the middle cohort that showed by far the largest ratio of follow-up variance accounted for by reactivity relative to initial baseline; the ratios were 0.13, 0.47, and 0.15, respectively. Further, a quite different pattern emerged from the analyses of upward drift in DBP; DBP reactivity was significantly associated with DBP drift in multivariate analysis for the middle and oldest cohorts, but not for the youngest cohort. Finally, age variations in the extent to which SBP reactivity predicted follow-up SBP differed between sexes; SBP reactivity predicted subsequent SBP in the youngest two male cohorts and in the oldest two female cohorts.

The results of a prospective study using change in carotid artery intima-media thickness over a 4-year follow-up period as outcome raise the possibility that the pathological implications of excessive BP reactivity may vary with socioeconomic position (6). In the present study, irrespective of whether the outcome was follow-up SBP or upward drift in SBP and DBP, reactivity was more strongly associated with outcome for participants from manual occupation households. Indeed, for SBP drift, SBP reactivity predicted approximately 5% of variance, not accounted for by age, BMI, and initial baseline SBP. It is reasonable to presume that with variations in socioeconomic position come variations in stress exposure (6) and that it is excessive reactivity in the context of high stress exposure levels that may be particularly toxic. There is some preliminary evidence to this effect. Cardiovascular reactions to stress have been observed in one study to predict 10-year follow-up BP primarily in those with high life-stress exposure (35). However, caution is warranted. If future BP status reflects the interaction of the magnitude of an individual’s reactions to stress and the extent of stress exposure, we might, in the present study, have expected more upward BP drift in the manual occupation group; this was not the case. Accordingly, it could be some other feature of low socioeconomic groups that makes high reactivity particularly predictive of future BP status.

It is possible to point to a number of limitations with the current study. First, there was high variability in resting, reactivity, and drift BPs. However, given the standardized procedures for measuring BP, this is unlikely to reflect measurement error. Further, other epidemiological studies of the same magnitude, such as Caerphilly (18) and Whitehall II (29), report similar SDs for BP. Second, given that there is evidence that family history of hypertension may interact with reactivity in predicting future blood pressure (35), the unavailability of information on family history did not allow us to test this particular interactive model of the etiology of high blood pressure.

In sum, the present results indicate that blood pressure reactions to stress predict future blood pressure status, and do so over and above the prediction afforded by initial resting BP, age, and BMI. Blood pressure reactions to stress were also associated with the extent of the upward drift in resting blood pressure over time. The prognostic implications of reactivity seem to be greater for those in lower socioeconomic positions and tend also to be greater for men than women.

Received for publication January 22, 2003.

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