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Psychosomatic Medicine 68:692-697 (2006)
© 2006 American Psychosomatic Society


ORIGINAL ARTICLES

Ethnicity, Perceived Discrimination, and Vascular Reactivity to Phenylephrine

KaMala S. Thomas, MS, Richard A. Nelesen, PhD, Vanessa L. Malcarne, PhD, Michael G. Ziegler, MD and Joel E. Dimsdale, MD

From the San Diego State University & University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California (K.S.T.); the Departments of Psychiatry (R.A.N., J.E.D.) and Medicine (M.G.Z.), University of California, San Diego, California; and the Department of Psychology, San Diego State University, San Diego, California (V.L.M.).

Address correspondence and reprint requests to Joel E. Dimsdale, MD, UCSD Mail Code 0804, La Jolla, CA 92093-0804. E-mail: jdimsdale{at}ucsd.edu


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Objectives: This study examined relationships among ethnicity, perceived discrimination, and vascular reactivity to phenylephrine (PE).

Methods: Seventy-six white patients and 46 black patients were studied at an inpatient clinical research center in response to a bolus intravenous injection of 100 µg PE. Self-report questionnaires assessed perceived discrimination.

Results: After controlling for body surface area, number of cigarettes smoked, and baseline blood pressure, black patients had greater vascular reactivity to PE than white patients (p = .01). There was also a significant relationship between perceived discrimination and diastolic blood pressure responsiveness to PE (p < .05). Path analyses revealed that perceived discrimination mediated the relationship between ethnicity and diastolic pressor responses. Individuals who perceived more discrimination had a larger increase in diastolic blood pressure in response to PE.

Conclusion: These data suggest perceived discrimination is associated with increased blood pressure responsiveness to PE.

Key Words: hypertension • ethnicity • blood pressure • reactivity • perceived discrimination

Abbreviations: BP = blood pressure; BSA = body surface area; HTN = hypertension; CVD = cardiovascular disease; PE = phenylephrine; SBP = systolic blood pressure; DBP = diastolic blood pressure; SEE = Scale of Ethnic Experience.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Black individuals have higher rates of hypertension (HTN) than people of any other ethnic group in the United States (1,2). Given the potent effect of life circumstances on blood pressure (BP) regulation, we wondered how perceived discrimination influenced BP in black and white individuals. Rather than measure BP alone, we examined one of the major underlying cardiovascular regulatory systems (i.e., pressor responses to an alpha agonist) in terms of perceived discrimination.

There is evidence that ethnic differences in HTN rates may partially be explained by greater exposure to chronic stressors among black individuals. One stressor that may be particularly relevant in accounting for BP differences between them is perceived discrimination.

Research examining the effects of perceived discrimination on BP demonstrates that black individuals who report more perceived discrimination have greater BP levels than those who perceive little or no discrimination (3–5). Furthermore, epidemiologic studies have demonstrated an association between perceived discrimination and HTN (5,6).

Although there is considerable evidence that perceived discrimination is a chronic stressor that has adverse effects on BP, relatively little work has examined the physiological pathways through which perceived discrimination may be associated with increased cardiovascular (CV) morbidity and mortality. Research suggests that high reactivity to stress is associated with the subsequent development of HTN (7,8); thus, it is surprising that few studies have examined the association between perceived discrimination and CV reactivity. Among those studies that have examined this association, findings suggest that perceived discrimination is associated with higher BP reactivity in black individuals (9–13). For instance, Armstead and colleagues (9) demonstrated that black individuals have greater increases in BP while watching film excerpts depicting racist situations than while watching films depicting anger-provoking, nonracist situations. Other studies have found higher BP reactivity to behavioral challenges among black individuals who report more exposure to racism (10,11,13). We wondered whether these reactivity differences would generalize to reactivity to pharmacologic challenge. Would individuals who perceived themselves as recipients of discrimination have greater BP reactivity to pharmacologic provocation?

Pressor sensitivity is a particularly interesting variable to examine in this context because it reflects how BP increases in response to a pharmacologic stimulus. By infusing phenylephrine (PE), an alpha-1 agonist that stimulates the same pressor receptors as norepinephrine, researchers can calculate pressor sensitivity. Research consistently demonstrates that this drug mimics the short-term effects of stress on BP by increasing vasoconstriction (14–16). Thus, examining pressor responsiveness to PE may provide a measure of an individual’s response to sympathetic nervous system activity.

Ethnic and racial differences in pressor sensitivity have been well documented. Research consistently demonstrates that black individuals have greater pressor responses to an alpha-1 agonist than white individuals (17–21). It is possible that this increased vascular reactivity to PE in black individuals can be explained by chronic stressors. In previous work, we examined how job strain was related to pressor sensitivity (22). In this article, we evaluate the role of perceived discrimination.

To date, no studies have examined the relationship between perceived discrimination and pressor responses to PE. Thus, we chose to extend the literature in this area. We hypothesized that black individuals would have a greater increase in BP in response to PE than white individuals. We also expected that there would be an interaction between perceived discrimination and ethnicity, with black individuals who perceive more discrimination having the highest pressor responses to PE.


    METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Participants
Sample characteristics are listed in Table 1. The study was conducted between July 2001 and July 2005. Participants consisted of employed (30+ hours/week) black and white men and women recruited for a study of stress and sympathetic nervous system activity from the local community through advertisement and referrals. As a result of these recruitment strategies, a total of 385 individuals contacted us and expressed interest in being in the study. Approximately 300 of these individuals responded to advertisements about the study and the rest were referred by physicians and previous participants. Of those who contacted us, 122 completed the study. Individuals who did not enroll in the study were not eligible (see subsequently for criteria), not interested in participating, or were unable to get time off work to be in the study.


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TABLE 1. Sample Characteristics by Race

 

Ethnicity was assessed by self-report. Forty-six of the participants were black (22 men and 24 women) and 76 were white (43 men and 33 women). Participants were between the ages of 25 and 52 with a body weight between 90% and 130% of ideal (Metropolitan life tables (23)) and resting BP lower than 180/110 mm Hg at screening. Screening BP was taken using Dinamap model 1846-SZ with appropriate-sized cuffs. BP readings were taken in the right arm by registered nurses and defined as the average of three seated BPs. Participants were recumbent and their hands were kept at heart level. They were instructed to refrain from moving their hand during the recording period. Individuals were excluded from the study if they had current drug or alcohol abuse, creatinine levels >1.4 mg/dL, renal bruit on physical examination, fasting glucose >120 mg/dL, known sleep disorder, shift work, or a medical diagnosis other than HTN. In addition, women were excluded if they were postmenopausal, diagnosed with premenopausal syndrome, taking oral contraceptives, or pregnant. Individuals with major medical conditions other than HTN or with a psychiatric disorder were excluded from the study.

Hypertensive patients taking antihypertensive medication were weaned off their antihypertensive medications and closely monitored. If their BP remained >140/90 but <180/110 mm Hg for 3 weeks, they were enrolled in the study. Before participation, informed consent was obtained in accordance with a protocol, which was approved by the University of California, San Diego, Institutional Review Board.

Measures
Scale of Ethnic Experience
The Scale of Ethnic Experience (24) is a 32-item, 5-point Likert-type self-report questionnaire that measures the experience of ethnicity across several dimensions. We conducted analyses using the "perceived discrimination" subscale. Perceived discrimination assesses whether an individual believes that members of his or her ethnic group have been discriminated against in society. Sample items include, "In my life, I have experienced prejudice because of my ethnicity," "My ethnic group does not have the same opportunities as other ethnic groups," and "I have not felt prejudiced against in American society because of my ethnic background." High scores on this subscale indicate greater endorsement of the construct being assessed. Internal consistency coefficients for the perceived discrimination subscale were 0.86 and 0.81 in a validation sample of black individuals and white individuals, respectively (24). The SEE was developed to be administered to individuals of any ethnic background. It was validated on a college sample from diverse ethnic groups and has been found to have sound psychometric properties with internal consistency coefficients ranging from 0.82 to 0.89 for the subscales and concurrent validity demonstrated through correlations with existing group-specific instruments in predicted directions.

Pressor Responses to Phenylephrine
The electrocardiogram (Hewlett-Packard 78352C) and Finapres BP (Ohmeda, 2300) signals were relayed to an A/D converter (Data Translation, DT2801), sampling at 1 kHz per channel (Global lab software, Data Translation) and stored in an IBM PC-compatible computer in 3-minute epochs. The BP cuff of the Finapres was placed on the third or fourth digit of the hand opposite the venous injection site. Hand position and cuff location were adjusted so that the Finapres readings were within 5 mm Hg of casual BP determinations. BP was recorded with the Finapres, a continuous BP monitor. Recording started with the injection of PE and continued for the next 3 minutes.

The subjects were tested for their response to PE in the Clinical Research Center in the afternoon. After resting supine for at least 20 minutes, baseline data were collected over the last 3 minutes of the 20-minute resting period. Immediately after baseline, a 100-µg PE bolus was administered intravenously. Pressor responses to PE were assessed by recording the changes in BP in response to PE. It was calculated as peak level BP in response to 100-µg PE dosage minus baseline BP (25–27).

Statistical Analysis
Data were analyzed using SPSS 11.0. Before conducting analyses, skewed pressor data were log-normalized. A multivariate analysis of variance was used to examine ethnic differences among the variables. Hierarchical regression analyses were then conducted to determine whether perceived discrimination predicted pressor responses to PE after controlling for ethnicity and other covariates. In these analyses, age, baseline BP, cigarette smoking, and body surface area (BSA) were included as covariates on block 1 of the model. Ethnicity was then entered on block 2 of the model. Perceived discrimination was entered on block 3 of the model. Finally, the interaction term of ethnicity x perceived discrimination was entered on block 4 of the model. To aid in interpretation of the interaction, ethnicity was coded as –1 (white individuals) and 1 (black individuals).

Secondary Analyses
To determine whether perceived discrimination mediated the relationship between ethnicity and diastolic pressor responses to PE, a mediational analysis was conducted using the method suggested by Baron and Kenny (28). According to Baron and Kenny (28), the following three conditions must be met to establish evidence for mediation. First, the predictor variable (ethnicity) must be related to the mediator (perceived discrimination). Second, the predictor variable must be related to the outcome variable (diastolic pressor responses to PE). Third, when the outcome variable is regressed onto both mediator and the predictor variable simultaneously, there should be a stronger association between the mediator and the outcome variable than between the predictor and the outcome variable. We tested these conditions in three steps using a series of regression analyses. To control for suspected covariates of pressor responses to PE, we entered age, BSA, baseline BP, and cigarette smoking on block 1 of the analyses.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Ethnic Differences
Ethnic differences in participant characteristics are listed in Table 1. Black individuals had a higher screening systolic blood pressure (SBP) (F1, 120 = 5.84, p < .05), baseline SBP (F1, 120 = 4.94, p < .05), and had a higher BSA than white individuals (F1, 120 = 8.94, p < .01). Black individuals also had a higher systolic (F1, 120 = 7.83, p < .01) and diastolic (F1, 120 = 7.17, p < .01) pressor response and reported more perceived discrimination (F1, 120 = 87.94, p < .01) than white individuals. Black individuals (N = 13) were more likely than white individuals (N = 7) to be diagnosed with HTN (F1, 120 = 4.23, p < .05). It is also noteworthy that hypertensives (mean, 3.31; standard error of mean [SEM], 0.19) perceived more discrimination than normotensives (mean, 2.71; SEM, 0.09) (F1, 120 = 6.8, p = .01).

Perceived Discrimination and Systolic Pressor Responses to Phenylephrine
Hierarchical regression analyses were conducted to determine the relationship between perceived discrimination and systolic pressor responses to PE after controlling for ethnicity and the covariates. Together, the covariates accounted for 5.3% of the variance in systolic pressor responses to PE (F = 1.05, not significant). After controlling for these covariates, ethnicity explained an additional 4.7% of the variance in systolic pressor responses to PE, with black individuals experiencing a greater increase in SBP in response to PE than white individuals ({Delta}F = 3.82, p = .05). Perceived discrimination was unrelated to systolic pressor responses to PE (see Table 2). Furthermore, there was no interaction between ethnicity and perceived discrimination on systolic pressor responses to PE.


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TABLE 2. Hierarchical Regression Analysis Summary for the Relationship Among Ethnicity, Perceived Discrimination, and Systolic Pressor Response to Phenylephrine

 

Perceived Discrimination and Diastolic Pressor Responses to Phenylephrine
Hierarchical regression analyses were conducted to determine the relationship between perceived discrimination and diastolic pressor responses to PE after controlling for ethnicity and the covariates. The covariates did not account for a significant amount of the variance in diastolic pressor responses to PE. Ethnicity explained an additional 7.0% of the variance in diastolic pressor responses to PE, with black individuals experiencing a greater increase in diastolic BP in response to PE than white individuals ({Delta}F = 5.6, p = .02). When perceived discrimination was entered on block 3 of the model, ethnicity no longer predicted diastolic pressor responses to PE (see Table 3). As can be seen in Figure 1, individuals who reported more discrimination experienced a greater increase in diastolic pressure in response to PE regardless of ethnicity ({Delta}R = 0.13.4, {Delta}F = 11.7, p < .01). There was no interaction between ethnicity and perceived discrimination on diastolic pressor responses to PE.


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TABLE 3. Hierarchical Regression Analysis Summary for the Relationship Among Ethnicity, Perceived Discrimination, and Diastolic Pressor responses to Phenylephrine

 

Figure 18
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Figure 1. Effects of ethnicity and perceived discrimination on diastolic pressor response. For visual purposes, perceived discrimination was dichotomized into high and low groups using median split. Individuals who perceive more ethnic discrimination have greater blood pressure responses to phenylephrine (p < .05).

 

Secondary Analyses
Because there was a significant relationship between perceived discrimination and diastolic pressor responses to PE, we wondered whether perceived discrimination mediated the relationship between ethnicity and diastolic pressor responses to PE. The following paragraphs summarize the results of regression analyses testing whether perceived discrimination mediates effects of ethnicity on diastolic pressor responses to PE. The covariates (age, cigarette smoking, BSA, and baseline BP) were controlled for in each step of the subsequent analyses.

Perceived Discrimination as a Mediator of Ethnicity and Diastolic Pressor Responses to Phenylephrine
Step 1: Ethnicity and Perceived Discrimination
Step 1 involved testing whether ethnicity predicted perceived discrimination. Analyses revealed that ethnicity was significantly associated with perceived discrimination (ß = 0.75, p < .001, r2 = 0.55).

Perceived Discrimination as a Mediator of Ethnicity and Diastolic Pressor Responses to Phenylephrine
Step 2: Ethnicity and Diastolic Pressor Responses to Phenylephrine
Step 2 involved testing whether ethnicity predicted diastolic pressor responses to PE. Covariates accounted for 2.5% of the variance in diastolic pressor responses to PE (F4, 118 = 0.50, not significant). Ethnicity accounted for 7.8% of the variance in diastolic pressor responses to PE (ß = 0.29, p < .05) (see Fig. 2A).


Figure 28
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Figure 2. Path model relating ethnicity and perceived discrimination to diastolic pressor responses to phenylephrine (PE). (A) The direct relationship between ethnicity and diastolic pressor responses to PE. (B) The indirect relationship between ethnicity and diastolic pressor responses to PE through perceived discrimination. After controlling for covariates (age, body surface area, cigarette smoking, baseline blood pressure), perceived discrimination mediated the relationship between ethnicity and diastolic pressor responses to PE.

 

Step 3: Ethnicity, Perceived Discrimination, and Diastolic Pressor Responses to Phenylephrine
There was a significant relationship between perceived discrimination and diastolic pressor responses to PE (ß = 0.39, p < .05). In the final step of the analysis, we entered perceived discrimination and ethnicity into the regression equation simultaneously. The full model accounted for 13.4% of the variance in diastolic pressor responses to PE (F6, 116 = 5.82, p < .01). There was complete mediation of the relationship between ethnicity and diastolic pressor responses to PE by perceived discrimination (ß = 0.42, p < .05). As can be seen in Figure 2B, when ethnicity and perceived discrimination were entered into the regression equation simultaneously, ethnicity no longer significantly predicted diastolic pressor responses to PE (ß = –0.04, p = .84). Regardless of their ethnicity, individuals who reported more discrimination had a larger diastolic pressor response to PE (r2 = 0.13).


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Studies have found that black individuals who report previous exposure to racism have higher BP levels (3–5) and greater CV reactivity to behavioral challenges (10,11,13). Based on these findings, we examined the relationship between perceived discrimination and pressor responses to PE in black individuals and white individuals. Although there was no association between perceived discrimination and systolic pressor responses to PE, there was a greater increase in diastolic BP in response to PE among individuals who reported more discrimination.

We expected that there would be an interaction between ethnicity and perceived discrimination such that black individuals who reported more discrimination would have the largest increase in BP when given PE. Interestingly, this was not the case in the current study. Although black individuals reported more discrimination than white individuals, the effect of perceived discrimination on pressor responses to PE was not limited to black individuals. Both black individuals and white individuals who reported more perceived discrimination had larger increases in BP in response to PE. In fact, secondary analyses revealed that perceived discrimination completely mediated the relationship between ethnicity and diastolic pressor responses to PE. This suggests that regardless of one’s ethnicity, stress from perceived discrimination may lead to increased sympathetic nervous system activation, possibly placing individuals at greater risk for developing cardiovascular disease. Stress activates the sympathetic nervous system, leading to increased norepinephrine and BP. The vasculature responds to increased BP by hypertrophy, resulting in thickened, muscular, and rigid blood vessels. Hypertrophied blood vessels respond to pressors such as norepinephrine and PE with exaggerated vasoconstriction. Thickened blood vessels also stretch poorly, causing impaired baroreflex activation. Black individuals are particularly susceptible to the development of HTN and thickened blood vessels. This scenario might explain the increased pressor responses to PE seen in black individuals and individuals who report higher levels of perceived discrimination. Longitudinal studies should be conducted to determine whether greater vascular reactivity found in individuals who report more perceived discrimination predicts the subsequent development of HTN.

PE is an alpha agonist that stimulates pressor receptors, leading to vasoconstriction and, in turn, increasing BP. In this study, we observed that the perception that one’s ethnic group is treated unfairly in society was associated with greater BP reactivity to PE. This effect was confined to diastolic pressor responses to PE. It has been posited that different types of stressors may operate on the body through different physiological pathways, uniquely affecting systolic and diastolic pressure. For instance, tasks that require active coping efforts may produce an increase in heart rate and systolic BP, whereas tasks that require quiet attentiveness and vigilance may lead to decreased cardiac output as well as increased total peripheral resistance and diastolic BP (29). Thus, our findings may suggest that individuals who perceive that members of their ethnic group are discriminated against have greater vascular reactivity, perhaps as a result of passive coping efforts and in the presence of increased vigilance to situations in which they might anticipate discrimination. However, it is important to note that these findings are correlational and do not imply cause and effect. Within the current study, it is impossible to determine whether perceived discrimination causes greater vascular reactivity as a result of passive coping efforts. Such conclusions would require longitudinal data, which are beyond the limits of our study.

This study examined associations among ethnicity, perceived discrimination, and pressor responses to PE in a sample of normotensive and hypertensive individuals. Thus, hypertensives were included in all analyses. However, we reconducted our analyses removing hypertensive individuals from the study and found that the results remained the same: perceived discrimination was associated with larger BP responses to PE. This suggests that perceived discrimination is associated with heightened BP responsiveness to provocation in both normotensive and hypertensive individuals. It goes without saying that HTN is multiply determined with important input from genetics, nutrition, and life experience. This article suggests that an additional facet of life experience (i.e., discrimination) may be relevant to BP. Larger samples would be necessary to ascertain with confidence particular settings in which discrimination may be particularly relevant (e.g., social class, job stress, one particular ethnic group).

The current results suggest that one physiological mechanism through which perceived discrimination is associated with increased HTN risk may be heightened pressor sensitivity. However, the risk may be affected by other factors such as obesity, low socioeconomic factors, and so on. These factors may interact with each other and increase HTN risk. For instance, individuals with heightened perception of discrimination may also be prone to obesity. We were reluctant to explore such questions because our sample size would be unstably small and results would be unreliable for such extended subgroup analyses. However, future research should examine how risk factors interact to predict heightened CVD risk. Addressing this issue may bring us closer to understanding why black individuals have particularly high rates of CVD morbidity and mortality.


    NOTES
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 

Received for publication January 3, 2006; revision received June 7, 2006.

DOI:10.1097/01.psy.0000238214.80871.e6


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 

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