(Stroke. 2001;32:1263.)
© 2001 American Heart Association, Inc.
Original Contributions |
Stress-Induced Blood Pressure Reactivity and Incident Stroke in Middle-Aged Men
Presented in part at the 57th Annual Scientific Meeting of the American Psychosomatic Society, Vancouver, British Columbia, Canada, March 17–20, 1999, and published in abstract form (Psychosom Med. 1999;61:125).
From the Department of Epidemiology, University of Michigan, Ann Arbor (S.A.E., J.W.L., G.A.K.); Research Institute of Public Health and Department of Community Health and General Practice, University of Kuopio (Finland) (T.A.L., J.T.S.); and Department of Neurology, University of Kuopio, and Brain Research and Rehabilitation Center, Neuron, Kuopio, Finland (J.S.).
Correspondence to Susan A. Everson, PhD, MPH, Department of Epidemiology, University of Michigan School of Public Health, 109 S Observatory St, Ann Arbor, MI 48109-2029. E-mail severson{at}umich.edu
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Abstract |
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Background and Purpose—Exaggerated blood pressure reactivity to stress is associated with atherosclerosis and hypertension, which are known stroke risk factors, but its relation to stroke is unknown. Previous work also indicates that the association between reactivity and cardiovascular diseases may be influenced by socioeconomic status.
Methods—The impact of blood pressure reactivity and socioeconomic status on incident stroke was examined in 2303 men (mean age, 52.8±5.1 years) from a population-based, longitudinal study of risk factors for ischemic heart disease in eastern Finland. Reactivity was calculated as the difference between blood pressure measured during the anticipatory phase of an exercise tolerance test (before exercise) and resting blood pressure, measured 1 week earlier. Mean systolic reactivity was 20 mm Hg (±15.9), and mean diastolic reactivity was 8.6 mm Hg (±8.5). Socioeconomic status was assessed as years of education. One hundred thirteen incident strokes (90 ischemic) occurred in 11.2 (±1.6) years of follow-up.
Results—Men with
exaggerated systolic reactivity (
20 mm Hg) had 72%
greater risk of any stroke (relative hazard ratio [RH], 1.72; 95%
CI, 1.17 to 2.54) and 87% greater risk of ischemic
stroke (RH, 1.87; 95% CI, 1.20 to 2.89) relative to less reactive men.
Moreover, men who were high reactors and poorly educated were nearly 3
times more likely to suffer a stroke than better educated, less
reactive men (RH, 2.90; 95% CI, 1.66 to 5.08). Adjustment for stroke
risk factors had little impact on these associations.
Diastolic reactivity was unrelated to stroke
risk.
Conclusions—Excessive sympathetic reactivity to stress may be etiologically important in stroke, especially ischemic strokes, and low socioeconomic status confers added risk.
Key Words: ischemia • reactivity • social class • stress • stroke
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferencesIntroduction References |
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Cardiovascular reactivity reflects underlying sympathetic nervous system activation and has been shown to vary according to individual characteristics (eg, personality factors, emotions), environmental exposures (eg, job stress, socioeconomic adversity), interpersonal and social contexts and interactions, and genetic predispositions to disease (eg, positive family history of hypertension or heart disease).1 2 3 4 5 Typically, this sympathetic hyperreactivity is manifest as excessive blood pressure (BP) or heart rate responses to psychological or behavioral stressors or stressful situations.5 Several human and animal studies support the hypothesis that exaggerated hemodynamic or cardiovascular reactivity to stress contributes to elevations in BP, carotid atherosclerosis, and coronary artery disease.6 7 8 9 10 11 12 13 Findings are not entirely consistent,14 15 however, with some evidence that the clinical significance of the association between reactivity and disease may be limited.16 Others have suggested that pathological consequences of reactivity may occur only in the presence of chronically stressful social environments.17
There are several recognized stroke risk factors, including hypertension, atherosclerosis, and atrial fibrillation. These risk factors are most strongly related to nonhemorrhagic stroke, and each involves arousal or activation of the autonomic nervous system, which suggests that sympathetic activation plays a role in stroke and particularly ischemic stroke. Thus, it stands to reason that stress-induced cardiovascular reactivity also may contribute to increased risk of stroke and especially stroke resulting from ischemia or ischemic mechanisms. To our knowledge, no prior population study has tested this hypothesis.
Stroke incidence and mortality are known to vary inversely
with socioeconomic
position.18 19 20
Similarly, as noted above, stress-induced reactivity varies by
environmental
exposures4 5 and
socioeconomic position, although the evidence linking stress-induced
reactivity and socioeconomic position is mixed. Carroll and
colleagues21 reported that
systolic BP (SBP) reactions to a psychological task (Raven’s
matrices) were positively related to occupational grade in a sample of
British male civil servants, whereas Gump et
al22 found that BP
reactivity to 2 
-adrenergic tasks (mirror tracing, cold pressor) was
greater in children and adolescents from socioeconomically
disadvantaged families (determined by the parents’ education and
occupations). The nature of the tasks used in these 2 studies may
account for the discrepancies in their results. Tasks that require
greater psychological engagement in order to perform well, such as
Raven’s matrices, which is a test of nonverbal intelligence, or
computer-oriented tasks, which may be intimidating to those without
computer experience, may elicit stronger cardiovascular
reactions among those who become differentially engaged in the
task.21 It is plausible that
such engagement could vary by educational level. On the other hand, it
has been hypothesized that the more adverse circumstances and chronic
stress typically experienced by those in lower socioeconomic strata may
contribute to exaggerated cardiovascular response to
stress.23 We previously have
reported that the effect of reactivity on progression of intimal-medial
thickening (IMT) is potentiated in men of lower socioeconomic status
(SES),24 which supports the
hypothesis that the impact of reactivity on disease depends in part on
one’s social environment and associated
stressors.17 Thus, it may be
that the relation of stress-induced reactivity to stroke also varies by
SES.
The present study investigated the relation between stress-induced BP reactivity and subsequent 11-year risk of stroke in a population sample of >2300 middle-aged men. Using data from the Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study, an ongoing study of biopsychosocial risk factors for cardiovascular disease, we were able to examine the independent effects of reactivity on stroke risk, after taking into consideration known risk factors for stroke. Secondarily, we examined joint effects of reactivity and SES on stroke risk.
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Subjects and Methods |
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Study Population
The KIHD Study is a comprehensive, population-based study of biological, socioeconomic, and psychosocial risk factors for atherosclerosis, heart disease, mortality, and other outcomes25 among middle-aged men from Kuopio, Finland, and surrounding rural communities in eastern Finland. Participants included 2682 men (82.9% of eligible), aged 42, 48, 54, or 60 years, who were enrolled between March 1984 and December 1989 (see details on the study protocol below). Subjects were excluded from the present analyses if they had a history of stroke (n=60), missing information on the measure of BP reactivity (n=255), or missing data on covariates (n=64), leaving a total of 2303 men eligible for the present study. (In regard to missing information on the measure of BP reactivity, because of scheduling conflicts, 255 participants were unable to participate in the bicycle ergometer stress test at the baseline examination. These men tended to be older and less educated (P<0.01), were more likely to be current smokers and to be taking antihypertensive medications at baseline (P<0.04), and had marginally higher resting SBP (P<0.07) than the 2303 participants included in the analyses.) Nonparticipants were older, less educated, and more likely to be current smokers and to take medications for hypertension and hypercholesterolemia (P<0.03) but did not differ from participants in terms of resting BP, fibrinogen, body mass index (BMI), alcohol consumption, LDL or HDL cholesterol, or prevalence of diabetes at baseline. Baseline subject characteristics are shown in Table 1
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Study Protocol
The baseline study consisted of 2 examination days,
separated by 1 week. Participants provided information on health
habits, including diet, smoking, and alcohol consumption, family and
personal history of disease, medications, SES, social support and
social networks, and various psychological characteristics.
Participants also underwent a medical examination, including
measurement of height, weight, percent body fat, and BP (see details
below), ultrasonographic assessment of carotid
atherosclerosis, and a bicycle ergometer maximal
exercise tolerance test. Lipids, hemostatic factors, and plasma glucose
and insulin, among other biochemical substrates, were determined from
venous blood samples obtained on the first examination day, after
overnight fasting and abstinence from smoking (12 hours), alcohol (3
days), and analgesics (7 days). Blood was drawn without tourniquet
after a 30-minute supine rest, with the use of Terumo Venoject VT-100
PZ vacuum tubes, and cooled immediately on ice (4°C).
Complete details of the KIHD Study protocol and recruitment procedures have been reported previously.25 The KIHD Study was approved by the University of Kuopio Research Ethics Committee and conducted according to their established guidelines for human research participants and data confidentiality.
Measurement of BP and Reactivity
The measurement protocol for assessing SBP and
diastolic BP (DBP) included a 15-minute supine rest with BP
measured 3 times at 5-minute intervals, a standing rest with 1 BP
reading taken after 1 minute, and a 10-minute seated rest with BP
measured twice at 5-minute intervals. Resting BP was measured on the
first examination day. The average of the 2 seated BP readings was
considered baseline resting BP. On the second examination day, 1 week
later, a second measure of sitting BP was obtained after the
participant had been seated on the bicycle ergometer for 5 minutes but
before the exercise test protocol was begun. Measurements on both
examination days occurred in the mornings. All BP readings were
obtained with a random zero sphygmomanometer by a trained
observer.
SBP and DBP reactivity were defined as the change in SBP and DBP in anticipation of the maximal exercise bicycle ergometer test relative to the average resting baseline BP obtained 1 week earlier. Research indicates that physiological, behavioral, and emotional arousal occurs in anticipation of exercise and its impending challenge.26 Consequently, elevations in BP during this anticipation phase are considered a measure of cardiovascular activation in response to psychological and behavioral stress, ie, cardiovascular reactivity.
Measurement of SES
Self-reported number of years of completed education
was used as the measure of SES. Because of the known association
between SES and stroke
risk,18 19 20
we also included education as a covariate in the risk factor–adjusted
model (modeled continuously) assessing the impact of reactivity on
stroke risk.
Ascertainment of Strokes
Stroke ascertainment was completed through December
31, 1997. Incident strokes that occurred during 1984–1992 were
ascertained through the FINMONICA stroke
register27 for this area and
classified according to the International
Classification of Diseases, Ninth Revision codes 430 to 438.
Data on strokes that occurred after 1992 were obtained from the
national hospital discharge registry via computerized linkage. A
neurologist (J. Sivenius) used these data to classify incident
strokes, using the same diagnostic criteria as FINMONICA.
Average follow-up time was 11.2±1.6 years.
Data Analyses
A series of Cox proportional hazards
models28 was used to assess
the relation between stress-induced BP reactivity and incident stroke.
Reactivity was modeled continuously and categorically (based on a
median split) in separate models. All models were adjusted for age and
resting SBP (resting DBP in models with DBP reactivity as the
predictor). Additional multivariate models included a
number of covariates representing known stroke risk
factors, including BMI, alcohol consumption, smoking, HDL and LDL
cholesterol, fibrinogen, SES, prevalence of diabetes, and
use of medication for hypertension or
hypercholesterolemia, as described below.
LOGISTIC and GLM procedures from SAS, version
6.12 (SAS Institute), were used for
analyses.
Assessment of Baseline Covariates
Age was modeled categorically with the use of
dummy-coded variables for ages 48, 54, and 60, with 42-year-olds as
the referent group. BMI was calculated as weight (kilograms) divided by
height (meters) squared and modeled continuously. Maximum oxygen uptake
(
O2max),
an indicator of fitness, was defined as the highest value of oxygen
uptake as measured by breath-by-breath respiratory gas exchange;
O2max
was modeled continuously. Resting SBP and DBP were calculated as the
average of 2 seated BP measurements (described above) and modeled
continuously. Cigarette smoking was determined by self-report and
modeled with a dummy-coded variable representing former
smokers and a continuous variable representing
pack-years for current smokers, with never smokers as the reference
group. Alcohol consumption was assessed by a questionnaire on drinking
behavior over the last 12 months and a 4-day dietary record and
modeled continuously as grams of ethanol per week. HDL and LDL
cholesterol levels were measured in millimoles per liter
and modeled continuously. Fibrinogen was measured in grams per liter
and modeled continuously. Use of medications for hypertension or
hypercholesterolemia, confirmed during the
medical examination, was modeled with dummy-coded variables.
Prevalent diabetes, confirmed if a participant reported currently using
diet or medication to control diabetes or if his fasting blood glucose
level was 6.7 mmol/L (120 mg/dL) was modeled with a dummy-coded
variable. (Self-reported history of and/or use of medication for
atrial fibrillation also was obtained at the baseline examination.
However, only 10 participants had a history of atrial fibrillation, and
none of these had a stroke during the follow-up. Consequently, we did
not include a covariate representing this risk factor in
our multivariate
models.)
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferencesIntroduction References |
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A total of 113 first strokes was identified during the 11 years of follow-up, with 90 of them determined to be ischemic or thrombotic, 21 determined to be hemorrhagic, and 2 undifferentiated. The average change in SBP in anticipation of exercise was 20 mm Hg (SD, 15.9; median, 19). The corresponding change in DBP was 8.6 mm Hg (SD, 8.5; median, 8). On average, participants reported 8.7 years (SD, 3.5) of education. Education was significantly, inversely related to both SBP (b, -0.49; t, -5.18; P<0.0001) and DBP changes (b, -0.15; t, -3.04; P<0.003) in anticipation of exercise.
All Strokes
A Cox proportional hazards model, with covariates for
age and resting SBP, found that each 1-mm increase in SBP in
anticipation of exercise corresponded to a significant 1-point increase
in risk of stroke (relative hazard ratio [RH], 1.01; 95% CI, 1.00 to
1.02). Dichotomizing respondents into high (greater than the
median) and low reactors (equal to or less than the median) showed that
men whose SBP rose >19 mm Hg in anticipation of exercise had a
72% greater risk of stroke over the subsequent 11 years than men who
were less reactive (P<0.006)
(Table 2). This association was modified only slightly
and remained significant after adjustments for age, resting SBP, SES,
smoking, alcohol consumption, BMI,
O2max,
LDL and HDL cholesterol, fibrinogen, history of diabetes,
and use of medication for hypertension or
hypercholesterolemia. Anticipatory
diastolic response was not related to increased stroke
risk.
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Reactivity and Stroke Risk by Type of
Stroke
The majority (79.6%) of incident strokes that occurred
in our population were due to ischemia or thromboembolism.
Analyses that limited the outcome to these nonhemorrhagic
strokes produced results similar to, albeit slightly stronger than,
those seen for all strokes combined. Each 1-mm increase in the
anticipatory SBP response corresponded to a significant 1.5% increased
risk of ischemic stroke (RH, 1.015; 95% CI, 1.00 to 1.03),
with adjustment for age and resting SBP. Modeling SBP reactivity
categorically showed that high reactors had 87% greater risk relative
to men who were less reactive in anticipation of exercise
(P<0.005)
(Table 2
). Inclusion of covariates representing
known stroke risk factors modified this association only slightly, with
high reactors demonstrating a significant 74% excess risk of
ischemic stroke in the fully adjusted model. DBP reactivity was
unrelated to ischemic strokes.
Neither SBP reactivity nor DBP reactivity was significantly related to risk of hemorrhagic stroke. However, relatively few strokes in our population were due to hemorrhage, and it is therefore likely that we did not have adequate power to reliably assess these associations.
SES, Reactivity, and Risk of Stroke
Because stroke incidence and mortality are typically
higher in lower SES
groups19 20 and
there is some evidence that cardiovascular reactivity
varies inversely with SES,22
we also sought to determine the joint effects of SBP reactivity and SES
on stroke risk. Education was significantly associated with stroke risk
in the multivariate model reported in
Table 2, with increasing education associated with
decreasing risk (RH, 0.90; 95% CI, 0.83 to 0.97). Subsequent
categorical analysis using approximate tertiles of education
corresponding to primary school or less (
6 years of school), some
vocational training or education beyond primary school but no high
school (7 to 8 years of school), and some high school or more (9
years of school) showed that the least educated men were at increased
risk of stroke (RH, 2.03; 95% CI, 1.22 to 3.37) relative to the best
educated men, but those with 7 to 8 years of education were not (RH,
1.33; 95% CI, 0.79 to 2.23).
Consequently, to assess the joint effects of SBP reactivity and education on risk of stroke, we conducted a set of Cox proportional hazards models that included terms representing the main effects of reactivity and education as well as their interaction for all strokes combined and for ischemic strokes. Reactor status was dichotomized by a median split of SBP response in anticipation of exercise, as above, and education was dichotomized as primary school or less versus greater than primary school on the basis of the aforementioned findings for education. The interaction term was the cross product of these 2 terms.
We did not observe a significant, multiplicative interaction
between reactor status and education for either all strokes combined
(RH, 0.75; 95% CI, 0.35 to 1.60) or ischemic strokes (RH,
0.93; 95% CI, 0.39 to 2.20). However, we did find significant main
effects for both reactor status and education (RH, 1.93; 95% CI, 1.15
to 3.26, and RH, 2.00; 95% CI, 1.09 to 3.67, respectively) with all
strokes as the outcome. Moreover, contrasting men with both risk
factors (high reactors with low education) with men with neither risk
factor showed that reactive men with the least education had the
greatest risk of stroke (RH, 2.90; 95% CI, 1.66 to 5.08) after
adjustment for age and resting SBP. With ischemic strokes as
the outcome, we observed a marginally significant main effect for
education (RH, 1.76; 95% CI, 0.87 to 3.55) and a significant main
effect for reactor status (RH, 1.90; 95% CI, 1.04 to 3.45) and again
saw the greatest risk of stroke in men with both risk factors (RH,
3.11; 95% CI, 1.67 to 5.77) compared with men with neither risk
factor. Risk factor adjustments produced only minor decrements in the
point estimates and thus showed little effect of confounding by known
stroke risk factors. For illustrative purposes, we have graphed the
risk factor–adjusted results of the contrasts between the 4 groups
that are identified by jointly considering reactor status and education
(Figure). Although the interaction term between
reactivity and education was not significant in our models, we believe
that it is informative to note the combined main effects of reactor
status and low education.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferencesIntroduction References |
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This study provides convincing evidence that exaggerated BP responses to stress contribute to increased risk of stroke and particularly stroke due to ischemia or thromboembolism in middle-aged and older men. The association between reactivity and incident stroke was modified very little by known risk factors for stroke. These data support the growing literature on the importance of hemodynamic or cardiovascular reactivity in the development and progression of cardiovascular diseases.6 7 10 11 To our knowledge, this is the first study to link reactivity to excess risk of stroke.
We also found that men who had limited education were at
greater risk of stroke than more educated men, which is
consistent with prior research showing an inverse socioeconomic
gradient for stroke incidence and
mortality.18 Education was
inversely related to reactivity in this study. Moreover,
analysis of the joint effects of low SES and reactivity on risk
of stroke showed that, while there was not a differential effect of
reactivity among the poorly educated men (ie, we did not observe a
significant statistical interaction between reactivity and education on
stroke risk), men with both risk factors in our study were nearly 3
times more likely to have had a stroke during the follow-up period
compared with men who had neither risk factor. These results suggest
that low SES adds to the risk of stroke associated with stress-induced
autonomic arousal. However, as noted and as shown in the
Figure,
both SES and reactivity uniquely contributed to excess stroke
risk.
In this study stress-induced reactivity was conceptualized and modeled as a characteristic of the individual. Indeed, we found that the most reactive participants had the greatest risk of stroke over the intervening 11 years of follow-up. Reactivity also may be conceptualized as a mediating mechanism by which psychological or social factors increase risk of cardiovascular disease.29 Our study was not designed to test this model. The fact that we found additive but not interactive effects in our analyses in which we modeled the joint effects of reactivity and low SES suggests that the characteristic of reactivity has significant, independent health effects. Moreover, demonstrating that stress-induced reactivity increases stroke risk is an important prerequisite to future studies that may seek to examine whether such reactivity mediates the relation between various psychosocial characteristics and stroke.
The inverse association between reactivity and SES observed here is consistent with the findings reported by Gump et al22 but in contrast to results reported by Carroll et al.21 Variations in our respective findings may very well relate to the types of tasks used, which differ in all 3 studies. For example, we have previously argued that the anticipatory period before exercise, the stressor used in the present study, can be characterized as a period of psychophysiological arousal attendant to an impending challenge6 and thus represents a measure of stress-induced reactivity. Differences between this reactivity measure and the type of cognitive task used in the study of Carroll et al may account for the discrepancies in our findings. It may be that tasks not dependent on scholastic achievement, in contrast to any number of verbal or nonverbal IQ tests, may yield more consistent results across studies. Additionally, as noted earlier, it is speculated that psychological engagement that influences task performance may influence the cardiovascular responses elicited and may vary by educational level. Other task characteristics, such as level of difficulty or salience to the participant, also may influence responses,5 30 although their relation to SES is unknown. Surprisingly few studies to date have directly examined the relation between cardiovascular reactivity and SES, and thus additional research is needed before firm conclusions can be made.
In the present study SBP reactivity in anticipation of exercise was related to greater stroke risk, whereas DBP reactivity was not. It is known that the sympathetic activation that occurs in the anticipatory phase before exercise is characterized by increased cardiac output without a compensatory decrease in vascular resistance.26 Moreover, SBP reactivity represents an acute increase in cardiac force during systole, whereas DBP reactivity reflects increases in resistance during diastole. Presumably, the pressor response patterns seen here in anticipation of exercise are representative of the sympathetic arousal experienced by these men to other emotionally stressful stimuli. Therefore, with repeated or prolonged exposure to stress, it may be that SBP reactivity and its accompanying increase in the rate and force with which blood is pumped into the vasculature exacerbates stroke risk by increasing the probability of an embolism.
Alternatively, the exaggerated SBP reactivity observed in this study may elevate the risk of stroke through general atherogenic mechanisms. For example, sympathetic arousal contributes to injury and dysfunction of the arterial endothelium, which may lead to formation of atherosclerotic plaques.13 31 In addition, neuroendocrine correlates of sympathetic nervous system activation, including increases in norepinephrine, epinephrine, and cortisol, can promote lipid mobilization32 33 and platelet activation, contributing to aggregation of platelets and formation of thrombi.34 Both of these processes also may exacerbate vascular injury and atherosclerotic plaque formation and progression.35 As noted previously, a well-recognized clinical complication of atherosclerosis is stroke.
We previously reported that the measure of stress-induced reactivity reported here is associated prospectively with increased risk of hypertension6 and progression of IMT7 in our population of middle-aged men from Finland. These certainly are plausible mechanisms by which reactivity increases risk of stroke. However, the design of our study does not make it possible to reliably test these hypotheses at this time. The earlier reports were based on the subset of participants who completed the baseline and 4-year follow-up examinations of the KIHD Study. Of the 2303 participants included in the present analyses, <38% completed the 4-year follow-up, and among these respondents, there have been too few incident strokes since the follow-up examination to adequately examine the importance of these stroke risk factors. Continued follow-up will enable us to better model causal pathways between stress-induced reactivity, changes in risk factors over time, and incident stroke.
A few limitations of our study need to be noted. First, the demographic makeup of the sample precludes widespread generalization of the findings. Our study sample consisted only of middle-aged white men. Research is needed in female, minority, and nonwhite populations to determine whether similar relationships exist between stress-induced reactivity and excess risk of stroke. Prior research suggests that there may be important differences in cardiovascular responses to stress according to sex and race or ethnicity.36 37 38 It is critical to determine whether these different patterns of response are differentially related to cardiovascular disease risk. Moreover, stroke morbidity and mortality are greater in minorities than in whites,39 emphasizing the need for research on risk factors for stroke in nonwhite populations.
A second limitation is that we did not gather data on the acute versus chronic experience of stress among our participants. Such information would be valuable given that prolonged exposure to stress, resulting in frequent and intense stress responses, is thought to be importantly related to the development and progression of disease.5 17
Our study also is limited by its inability to address the relation between stress-related reactivity and hemorrhagic stroke. A larger number of hemorrhagic strokes than occurred in our study population would be required to adequately assess the association between stress-induced cardiovascular reactivity and hemorrhagic strokes.
In summary, this study provides new epidemiological evidence of a link between stress-induced BP reactivity and an important clinical cerebrovascular end point in a population sample of middle-aged men. Additional research is needed to corroborate these findings in other populations, particularly in women and minorities. This is an important area of research to pursue, given the increasing prevalence of stroke in our aging population.40 Our findings add to the literature that seeks to further our understanding of the critical role that stress plays in the development and progression of atherosclerosis and its clinical complications.
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Acknowledgments |
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This study was supported by a Scientist Development Award from the American Heart Association; grant HL44199 from the National Heart, Lung, and Blood Institute; grant AG13199 from the National Institute of Aging; and grants from the Academy of Finland and the Finnish Ministry of Education. Dr Lakka was supported by grants from the Yrjö Jahnsson Foundation and the Juho Vainio Foundation, and Dr Salonen was an Academy Professor of the Academy of Finland.
Received August 31, 2000; revision received November 15, 2000; accepted March 15, 2001.
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Editorial Comment
Something Old and Something New
Presented in part at the 57th Annual Scientific Meeting of the American Psychosomatic Society, Vancouver, British Columbia, Canada, March 17–20, 1999, and published in abstract form (Psychosom Med. 1999;61:125).
Department of Psychiatry, Epidemiology, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferencesIntroduction References |
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When considered separately from other cardiovascular diseases, stroke ranks as the third leading cause of death. It is a leading cause of serious, long-term disability in the United States.R1 Identification of new risk factors holds promise for prevention of stroke’s substantial public health burden.
A longstanding hypothesis, called the
cardiovascular reactivity hypothesis, is that
individuals who show frequent, large blood pressure and heart rate
responses to psychological stress experience recurrent sympathetic
activation, which increases risk for atherosclerosis
and perhaps hypertension.R2 In
the preceding article, Everson and her colleagues tested the hypothesis
for the first time in relation to risk for stroke in a population-based
study of men, the Kuopio Ischemic Heart Disease Risk Factor
Study (KIHD). Their measure of stress-induced changes in
cardiovascular reactivity was a systolic blood
pressure (SBP) rise in anticipation of an exercise tolerance test.
Anticipatory blood pressure rise predicted incident strokes, especially
ischemic strokes. Furthermore, the association remained
significant after adjustment for age,
O2max,
education, resting blood pressure, smoking, alcohol consumption, body
mass index, lipids, fibrinogen, use of medications for hypertension and
hypercholesterolemia, and history of diabetes.
The findings are impressive, considering their novelty, careful
ascertainment of cases, and thorough assessment of possible covariates.
Once again, KIHD has served as an important resource for testing social
and psychological hypotheses about risk for
cardiovascular disease.
The assumption underlying the measurement of reactivity in KIHD is that men who showed a large SBP rise before their maximal exercise test were experiencing psychological stress and would show large SBP rises in a variety of other stressful circumstances. The next step in this research would be to confirm that assumption. Highly standardized and reliable measures of cardiovascular changes in response to diverse mental and physical challenges, eg, serial subtraction and cold pressor, are available to test the reactivity hypothesis.R3 It is unknown how the SBP rise in anticipation of exercise tolerance testing relates to more conventional measures of reactivity and how reproducible it is. Blood pressure changes during exercise predict hypertension,R4 and blood pressure rises before exercise stress testing predict hypertension in KIHD.R5 It is important to evaluate how the anticipatory SBP exercise response relates to accompanying hemodynamic and neuroendocrine changes, to the blood pressure response during exercise, and to total blood pressure burden via ambulatory blood pressure measurement. In this way, a more precise and generalizable interpretation of the present results can be made, results from ongoing epidemiological studies can be compared, and the best indicators of cardiovascular reactivity can be used as a diagnostic tool for stroke risk. It may be that a simple measure of SBP rise before exercise stress testing will be the most useful clinically, but we do not know yet.
Low socioeconomic status (SES) is a well-established predictor of cardiovascular diseases, including stroke,R6 but the reason for this is not completely understood. Possible SES links involving cardiovascular reactivity to stress are that individuals from lower SES are more likely to respond to the same psychological stressors with larger cardiovascular responses than are higher SES individuals; low SES individuals are exposed to more frequent and severe psychological stressors, such that with other things being equal, they experience more frequent sympathetic nervous system activation; or that they experience more stressors and are more likely to be reactive to those stressors. The present study tested the first pathway and found that less-educated men showed greater rises in SBP before exercise. However, assuming that SES is in part a proxy for stress exposure, analyses testing the last pathway (whether less-educated men who were reactive to stress were at a particular disadvantage for stroke) did not reveal an interactive effect. Everson and her colleagues report the familiar and independent effect of education: men who were less educated had twice the risk of stroke relative to better-educated men. Educational attainment may not confer substantial advantage through any single risk factor, including cardiovascular reactivity. Rather, the health benefits of education may rest on the accumulation of lifelong exposures to multiple risk factors as well as on the resources for adapting to later life’s inevitable challenges.
So we have something old and something new in this article. Yet again, education remains a powerful predictor of stroke incidence, and we don’t know entirely why. Strong evidence is marshaled for a new risk factor for stroke: cardiovascular reactivity to psychological stress. This article encourages further testing of cardiovascular reactivity to mental stress in populations most vulnerable to stroke in the United States: elderly women, African Americans, and American Indians/Alaska natives.
Received August 31, 2000; revision received November 15, 2000; accepted March 15, 2001.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferencesIntroduction References |
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1. American Heart Association. Heart and Stroke Statistical Update. www.americanheart.org/statisticas/stroke.html. Accessed April 21, 2001.
2. Matthews KA, Weiss S, Detre T, Demobroski T, Falner B, Manuck S, Williams R, eds. Handbook of Stress, Reactivity, and Cardiovascular Disease. New York, NY: John Wiley & Sons; 1986.
3. Kamarck TW, Jennings JR, Manuck SB. Psychometric applications in the assessment of cardiovascular reactivity. Homeost Health Dis. 1993;34:229–243.
4. Pickering TG, Gerin W. Cardiovascular reactivity in the laboratory and the role of behavioral factors in hypertension: a critical review. Ann Behav Med. 1990;12:3–16.
5. Everson SA, Kaplan GA, Goldberg DE, Salonen JT. Anticipatory blood pressure response to exercise predicts future high blood pressure in middle-aged men. Hypertension. 1996;27:1059–1064.
6. Kunst AE, del Rios M, Groenhof F, Mackenback JP, for the European Union Working Group on Socioeconomic Inequalities in Health. Socioeconomic inequalities in stroke mortality among middle-aged men. Stroke. 1998;29:2285–2291.\.
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