Psychosomatic Medicine Tips for Better Browsing
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sherwood, A.
Right arrow Articles by Hinderliter, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sherwood, A.
Right arrow Articles by Hinderliter, A. L.
Psychosomatic Medicine 66:507-513 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

Hostility Is Related to Blunted ß-Adrenergic Receptor Responsiveness Among Middle-Aged Women

Andrew Sherwood, PhD, Joel W. Hughes, PhD, Cynthia Kuhn, PhD and Alan L. Hinderliter, MD

From the Department of Psychiatry and Behavioral Sciences (A.S., J.W.H.), Department of Pharmacology (C.K.), Duke University Medical Center, Durham, NC; and Department of Medicine (A.L.H.) at the University of North Carolina, Chapel Hill, NC.

Address correspondence and reprint requests to Andrew Sherwood, Ph.D., DUMC-3119, Durham, NC 27710. E-mail: sherw002{at}mc.duke.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: Based on previous findings in men, the hypothesis that hostility would be associated with blunted responsiveness of cardiovascular ß-adrenergic receptors was tested in a study sample of middle-aged women. The roles of the sympathetic nervous system and of social support in this putative relationship were also evaluated.

METHODS: Subjects were 80 healthy women (n = 23 African American; n = 57 white), aged 47 to 55 years. Hostility was assessed using the Cook-Medley Hostility Scale and social support was assessed with the Brief Social Support Questionnaire. Intravenous isoproterenol challenge was used to evaluate cardiac and vascular ß-adrenergic receptor responsiveness. Twenty-four-hour urinary catecholamine excretion was used to index sympathetic nervous system activity.

RESULTS: Hostility was related to blunted cardiac (R = 0.33, p < .01) and vascular (R = 0.23, p < .05) ß-adrenergic receptor responsiveness in simple correlation analysis and in hierarchical regression analyses controlling for race, menopausal status, weight, and resting heart rate. Low social support was also related to blunted ß-adrenergic receptor responsiveness (R = 0.3, p < .01). Twenty-four-hour norepinephrine excretion was related both to hostility (R = 0.32, p < .01) and to cardiac (R = 0.25, p < .05) and vascular (R = 0.24, p < .05) ß-adrenergic receptor responsiveness.

CONCLUSIONS: These observations replicate and extend previous findings in men by demonstrating that higher levels of hostility and low levels of social support are associated with blunted ß-adrenergic receptor responsiveness in middle-aged women. They also suggest that heightened sympathetic nervous system activity associated with hostility may contribute to ß-adrenergic receptor blunting. Because blunted ß-adrenergic receptor sensitivity is a characteristic feature of a broad range of cardiovascular diseases, these findings may reflect an early preclinical manifestation of pathophysiology accompanying hostility and low social support.

Key Words: adrenergic receptor responsiveness, • Cook-Medley Hostility, • social support, • catecholamines, • menopause.

Abbreviations: AR = adrenergic receptor;; CD25 = chronotropic dose of isoproterenol required to increase HR by 25 bpm;; DBP = diastolic blood pressure;; ECG = electrocardiogram;; Ho = Cook Medley Hostility scale;; HR = heart rate;; MAP = mean arterial pressure;; PD25 = dose of phenylephrine required to increase MAP by 25 mm Hg;; SBP = systolic blood pressure;; SSQ = Sarason Brief Social Support scale;; SVR = systemic vascular resistance;; VD40 = vasodilatory dose of isoproterenol required to decrease SVR by 40%.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Exaggeratedsympathetic nervous system (SNS) activity among hostile individuals (1–4) may help to explain why hostility is a risk factor for coronary heart disease (CHD) (1,5–10). Consistent with the effects of SNS overactivity, several recent studies have related hostility to cardiovascular ß-adrenergic receptor (ß-AR) downregulation. Among men, hostility assessed with the Cook-Medley Hostility (Ho) scale (11) has been associated with downregulation of ß-ARs assessed using mononuclear leukocyte ß-AR density and responsiveness (12). Hostility also has been associated with down-regulation of cardiac ß-ARs and vascular ß-ARs assessed by heart rate (HR) and systemic vascular resistance (SVR) responses to infused isoproterenol (13,14). Heightened sympathetic activity, indexed by elevated catecholamine levels, measured in plasma or urine, has been related to ß-AR downregulation (15,16). However, there have been no studies to date that have evaluated whether reduced ß-AR sensitivity associated with hostility is mediated by elevated catecholamines.

The present study was designed to extend our prior observations in a number of ways. First, we sought to determine whether the relationship between hostility and blunted ß-AR responsiveness would be evident in a sample of middle-aged women, an age at which there is a marked rise in cardiovascular disease risk for women (17). A second study objective was to test the hypothesis that elevated urinary catecholamines might contribute to blunted ß-AR responsiveness associated with hostility. Finally, we sought to replicate our previous exploratory observation that low social support was related to blunted ß-AR responsiveness (13).


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Participants
A total of 80 healthy women (n = 23 African American; n = 57 white), aged 47 to 55 years (M = 50.2, SD = 2.1) comprise the study sample of the current report. Participants were recruited by advertisements in local newspapers. Women who reported regular menstruation were considered premenopausal and women who had not menstruated in at least 9 months were considered postmenopausal. Perimenopausal women and women taking hormone replacement therapy were excluded. The participants were 53% postmenopausal and 47% premenopausal. Demographic characteristics are summarized in Table 1. Other exclusion criteria included uncontrolled hypertension (systolic blood pressure [SBP] > 179 mm Hg or diastolic blood pressure [DBP] > 99 mm Hg), surgical menopause, current prescription cardiovascular medications, and use of tobacco products. The study protocol was reviewed and approved by Duke University Medical Center’s Internal Review Board, and all participants provided verbal and written consent before participation.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Characteristics of Study Sample (Mean ± SD)
 
Psychosocial Measures
Hostility was assessed using the Cook-Medley Hostility Scale (11). This 50-item true/false questionnaire was derived from the Minnesota Multiphasic Personality Inventory and has shown acceptable psychometric characteristics validity (18). The Ho scale has been prospectively related to coronary heart disease and angiographically determined severity of atherosclerosis (1). Perceived social support satisfaction was assessed using the Sarason Brief Social Support scale (SSQ) (19). The Brief Social Support Questionnaire measures the number of perceived providers of social support for six common support scenarios, yielding a perceived availability score (SSQ Availability), as well as satisfaction with the perceived social support, yielding a satisfaction score (SSQ Satisfaction). Both scales for this measure have demonstrated internal consistency exceeding 0.9, adequate validity, and near equivalence with the full 27-item version of the Social Support Questionnaire (19,20). Hostility was negatively correlated with both perceived availability of social support (r = –0.33, p < .01) and perceived satisfaction with social support (r = –0.33, p < .01).

Cardiovascular Measurements During Receptor Responsiveness Testing
All receptor responsiveness testing was conducted while participants were reclined and at least 6 hours after the most recent caffeine consumption. Blood pressure was measured continuously using the Finapres Model 2300 (Ohmeda, Madison, WI) noninvasive blood pressure monitor, which uses the vascular unloading technique to measure systolic, diastolic, and mean blood pressure on a beat-by-beat basis. This instrument has been validated against intraarterial measures under various conditions including pressor responses to phenylephrine (21). HR was derived from the electrocardiogram (ECG) as the interval between successive R-waves. Impedance cardiography was used to measure cardiac output (CO) (22). A tetrapolar band electrode configuration was used in conjunction with a Minnesota Model 304B impedance cardiograph (Surcom, Minneapolis, MN) to record impedance dZ/dt and Zo signals. Computer ensemble averaging software (COP_WIN, Bio-Impedance Technology, Inc., Chapel Hill, NC) was configured to derive CO every 10 seconds. Mean arterial pressure (MAP) averaged over corresponding 10-second intervals was used to derive systemic vascular resistance (SVR), according to the equation: SVR (dyne-sec.cm-5) = (MAP/CO)*80).

Resting Blood Pressure and Heart Rate Measurements
Resting systolic blood pressure, diastolic blood pressure, and HR were assessed during a 20-minute baseline rest period, during which participants sat in a comfortable recliner chair in a sound-attenuated, electrically shielded room. Blood pressure measurements were obtained every 5 minutes during the first 15 minutes, and were repeated every minute during the final 5 minutes. The last 5 readings were averaged to represent resting blood pressure. Blood pressure was measured utilizing a Suntech 4240 monitor. The ECG was used to derive resting HR.

ß-Adrenergic Receptor Responsiveness
The standardized isoproterenol sensitivity test was used to evaluate cardiac ß-adrenergic receptor responsiveness in terms of the chronotropic dose of isoproterenol required to increase HR by 25 bpm (CD25) (23). Progressively increasing bolus-doses of isoproterenol (0.125, 0.25, 0.5, 1.0, 2.0, 4.0 µg) were injected into an antecubital vein until an increase in HR of at least 25 bpm was observed. HR responses after each dose were computed as the shortest three successive ECG R-R intervals after drug injection, compared with the shortest three R-R intervals at rest (preinjection). After each dose, the next higher dose was not injected for at least 5 minutes, or until cardiovascular activity had returned to resting levels, usually within 5 to l0 minutes. The linear regression model of log-dose/HR response for each subject was used to determine CD25 exactly by interpolation. The CD25 measure provides an index of cardiac ß1 and ß2 receptor responsiveness, and is inversely related to ß-adrenergic receptor responsiveness. Vascular ß2-adrenergic responsiveness was also estimated by determining the vasodilatory dose of isoproterenol required to lower SVR by 40% (VD40). This index of vascular ß2-adrenergic responsiveness, which we have reported in our previous studies (24), is also inversely related to receptor responsiveness.

{alpha}1-Adrenergic Receptor Responsiveness
A procedure analogous to the ß-responsiveness test described above was used for assessing {alpha}1 adrenergic receptor responsiveness, using the {alpha}1 agonist phenylephrine to stimulate vascular {alpha}1 adrenergic receptors (25). In this test, the criterion response is defined as the dose required to increase mean arterial pressure by 25 mm Hg (PD25). An initial dose of 25 µg phenylephrine was used, with successive doses doubled until the 25 mm Hg response was exceeded, or until a maximum dose of 800 µg. Again, at least 5 minutes, or longer if required for recovery of cardiovascular activity to resting levels, preceded administration of successive doses. The linear log-dose/MAP response curve was used to determine the exact PD25 dose. The PD25 index is inversely related to vascular {alpha}1 receptor responsiveness.

24-Hour Urine Catecholamine Measurement
Participants collected a 24-hour urine sample on a weekday, within 1 week of all other assessments. Urine samples were kept in a portable cooler with ice packs throughout the 24-hour sample period and were returned after conclusion of the last collection. Urinary levels of epinephrine and norepinephrine were determined by high-pressure liquid chromatography (HPLC) with electrochemical detection. Levels of 24-hour urinary epinephrine (E24) and norepinephrine (NE24) were indexed for body surface area (BSA) to control for body size and expressed as ng/BSA. Urine creatinine was determined using kits supplied by Sigma Chemical Co. (St. Louis, MO). To guard against poor compliance with 24-hour urine collection, 24-hour creatine excretion was compared against normative ranges, using published algorithms based on gender, ethnicity, and body size (26). Only participants demonstrating good compliance, using this quality control step, were included in this report. This quality control step resulted in the elimination of 4 participants from catecholamine analyses due to incomplete urine collections.

Statistical Analyses
The association of hostility and social support with {alpha}- and ß-AR responsiveness was investigated with bivariate measures of association and hierarchical multiple linear regression analyses. First, simple correlations between scores on psychological measures and the CD25 and PD25 measures of ß- and {alpha}1-AR responsiveness were computed. Separate hierarchical multiple linear regressions were then conducted to examine the ability of 24-hour catecholamines, hostility, and social support to predict CD25, VD40, and PD25 after controlling for race, menopause status, weight, and age. Categorical variables were dummy coded. Correlations and hierarchical multiple regressions were used to evaluate the hypothesis that any observed relationship between hostility and ß-AR responsiveness was associated with 24-hour catecholamines. All statistical analyses were performed using SAS software (SAS, Cary, NC). All omnibus tests were considered statistically significant if p < .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
{alpha}-Adrenergic Receptor Responsiveness
Ho, SSQ Availability, and SSQ Satisfaction scores were not correlated with the PD25 measure of {alpha}-adrenergic responsiveness (Table 2, r values < 0.03, p values > .86). Hierarchical regression analyses performed to further examine possible associations of Ho and SSQ with PD25 (while controlling for race, menopause status, weight, and age) also yielded negative findings.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Simple Correlations Between Psychosocial and Sympathetic Nervous System Measures
 
Cardiac ß-Adrenergic Receptor Responsiveness
Ho scores were positively correlated with the CD25 measure of ß-adrenergic responsiveness (Table 2, r = 0.33, p = .003), and SSQ Satisfaction scores were negatively related with CD25 (r = –0.35, p = .002). SSQ Availability scores were not related to CD25 (r = –0.18, p = .11).

Hierarchical regression analyses were performed to test the hypotheses that Ho and SSQ Satisfaction scores would be related to cardiac ß-adrenergic receptor responsiveness (CD25) after controlling for other possible predictors (Table 3). The first step regressed CD25 on the linear combination of race, menopause status, weight, age, and resting HR (Step I, Table 3). The equation containing these variables accounted for 27% of the variance in CD25 [F(5,70) = 5.14, p < .001, adjusted R2 = 0.22]. Significant beta weights were observed for age (p = .04) and weight (p < .0001), as well as a trend for resting HR (p = .10). In Step II of the analyses, Ho scores and SSQ Satisfaction scores were each added to the model in separate regression equations. When Ho was added to the model (Step II, Model 1), an additional 9.3% of the variance was explained [{Delta}R2 = 0.09, F(1,69) = 10.07, p = .002]. To illustrate the association of hostility and ß-AR responsiveness, values of CD25 for high and low hostile groups defined by median split on Cook Medley Ho scores (Ho median = 13) are presented in Figure 1. When SSQ Satisfaction was added to the model (Step II, Model 2), an additional 4% of the variance was explained, which was only a marginally significant effect [{Delta}R2 = 0.04, F(,69) = 3.6, p = .06]. As shown in Table 3 (Step III Model 1), when SSQ was added to the model containing Ho, it was a nonsignificant factor (p > .3), whereas Ho remained a significant (p = .01) determinant of CD25.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Hierarchical Regression Analyses Predicting CD25 (µg)
 


View larger version (15K):
[in this window]
[in a new window]
  		Figure 1. Cardiac (CD25: µg isoproterenol) and vascular (VD40: µg isoproterenol) ß-adrenergic receptor responsiveness for High and Low Hostile groups by median split on Ho scores. Note: The CD25 and VD40 indices are inversely related to ß-adrenergic receptor responsiveness.

 
Vascular ß-Adrenergic Receptor Responsiveness
Ho scores were positively correlated with the VD40 measure of ß-adrenergic responsiveness (Table 2, r = 0.23, p < .05), and SSQ Availability scores were negatively correlated with VD40 (r = –0.30, p < .01), whereas SSQ Satisfaction scores were unrelated to VD40 (r = –0.14, p > .1).

Parallel hierarchical regression analyses to those described above for CD25 were performed to test the hypotheses that Ho and SSQ Availability scores would be related to vascular ß-adrenergic receptor responsiveness (VD40). Step 1 regressed VD40 on the linear combination of race, menopause status, weight, age, and resting SVR, accounting for 12% of the variance in VD40 [F(5,67) = 0.19, p = .1, adjusted R2 = 0.06]. A significant beta weight was observed only for weight (p < .05). When Ho was added to the model (Step II, Model 1), an additional 7% of the variance was explained [{Delta}R2 = 0.09, F(1,66) = 5.48, p = .02]. Values of VD40 for high and low hostile groups defined by median split on Cook Medley Ho scores (Ho median = 13) are presented in Figure 1. When SSQ Availability was added to the model (Step II, Model 2), an additional 5% of the variance was explained [{Delta}R2 = 0.05, F(1,66) = 4.0, p = .05]. However, in Step III, when SSQ was added to the model containing Ho, it was a nonsignificant factor (p > .2).

NE24, Hostility, and ß-Adrenergic Receptor Responsiveness
To test the hypotheses that the relationship between hostility and CD25 and VD40 may be attributable to elevated SNS activity, 24-hour urinary catecholamine excretion levels, E24 and NE24, were first correlated with Ho scores and CD25 values (Table 2). Ho scores were related to NE24 values (r = 0.36, p = .001), and NE24 was related both to CD25 (r = 0.25, p < .05) and VD40 (r = 0.24, p < .05) satisfying the minimal conditions necessary to consider whether NE24 might account for the relationship between hostility and CD25 and VD40. E24 values were unrelated to Ho scores and CD25 and VD40 values, and were not considered further.

For the evaluation of CD25, NE24 was entered into a hierarchical regression model that included race, menopause status, weight, age, and resting HR (Table 4, Steps I and II). The baseline variables accounted for a cumulative 25.8% of the variance in CD25 [F(5,65) = 6.24, p < .0001, adjusted R2 = 0.31], but the addition of NE24 improved the prediction of CD25, accounting for an additional 11% of the variance [{Delta}R2 = 0.107, F(1,65) = 10.95, p < .0001]. In Step III, Ho scores were entered to determine whether Ho remained an independent predictor of CD25 after controlling for NE24 values. Although Ho remained a significant predictor of CD25, it now accounted for only 4% of the variance in CD25 [{Delta}R2 = 0.041, F(1,64) = 4.44, p = .04], in contrast to 9% in the absence of NE24 (shown in Table 3, Step II Model 1).


View this table:
[in this window]
[in a new window]
  		TABLE 4. Hierarchical Regression Analyses Predicting CD25 (µg)
 
Similarly for VD40, NE24 was entered into a hierarchical regression model that included race, menopause status, weight, age, and resting SVR. The baseline variables accounted for a cumulative 11% of the variance in VD40 [F(5,64) = 1.59, p = .18], but in Step II the addition of NE24 improved the prediction of VD40, accounting for an additional 8% of the variance [{Delta}R2 = 0.083, F(1,63) = 6.5, p < .02]. In Step III, when Ho scores were entered after controlling for NE24, Ho now accounted for only 2% of the variance in VD40 and was a nonsignificant predictor [{Delta}R2 = 0.021, F(1,62) = 1.69, p = .04], whereas NE24 remained a significant predictor (F(1,62) = 6.57, p < .02) in the presence of Ho, and continued to account for more than 8% of the variance in VD40.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
The results of this study add to the growing evidence that hostility is associated with blunted cardiovascular ß-AR responsiveness. These findings are consistent with our previous observations for men (13,14), and they represent the first evidence that hostility is associated with blunted ß-AR responsiveness among women. The specificity of the association of hostility with adrenergic receptor function is again underscored by the observed lack of any association between hostility and cardiovascular {alpha}-AR function. To our knowledge, the present study is also the first to demonstrate that elevated SNS activity may play a role in the relationship between hostility and blunted ß-AR responsiveness. Twenty-four-hour urinary norepinephrine excretion was correlated both with hostility scores and with CD25 and VD40, and norepinephrine accounted in part for the association between hostility and these indices of cardiac and vascular ß-AR responsiveness.

SNS hyperactivity has been demonstrated to cause ß-AR down-regulation in animal models, and is considered the primary mechanism for ß-AR blunting in human cardiovascular disease (27,28). Blunted ß-AR responsiveness is implicated in the pathophysiology of hypertension (24,25,29–31), and is impaired in ischemic heart disease (32,33) and left ventricular hypertrophy (34). In congestive heart failure (CHF), blunted ß-AR responsiveness is a pathophysiologic feature contributing to the severely compromised cardiac function that characterizes the disease (35,36). Protection of the ß-AR system from SNS overstimulation by ß-blocking drugs has emerged as the intervention of choice for a variety of cardiovascular diseases, including CHD and CHF, where their protective effects are associated with a reduction in morbidity and improved life expectancy (37,38). ß-AR blunting in otherwise healthy individuals may be an early marker of pathophysiology, and a useful model for understanding factors involved in the etiology of cardiovascular disease.

SNS hyperarousal and consequent ß-AR blunting may help to explain why hostile individuals are at increased risk of developing cardiovascular disease, and why hostile cardiac patients are at increased risk of mortality (6–10,39). Hostile individuals have been found to show abnormally elevated catecholamine levels during laboratory stressors (2,4). Individuals high in hostility are also more likely to experience higher levels of chronic stress because of their greater propensity for interpersonal conflict (1). Our evidence of elevated 24-hour catecholamine excretion associated with hostility is consistent with the notion of higher daily stress in hostile individuals, and the observed down-regulation of cardiovascular ß-ARs in our study sample of healthy women is likely secondary to what may reflect chronic SNS arousal in the more hostile, but otherwise healthy women. In our previously reported study examining the phenomenon in women, we found hostility to be unrelated to cardiac ß-AR responsiveness (13). One possible explanation for this discrepancy is that women in the present study were older (48–55 years), with approximately half postmenopausal; whereas the women in our prior study (13) were younger (25–45 years) and all premenopausal. Heart disease in premenopausal women typically is manifest approximately 12 to 15 years later than in men; after menopause this age gap closes rapidly (40). Indeed, CD25 was considerably higher in the present study sample (2.9 ± 1.8) compared with the women in our previous study sample (1.8 ± 1.1), and notably more similar to the 25- to 45-year-old men in the earlier study. Resistance to cardiovascular disease in younger women may include protection from the psychosocial risk factors that may dramatically emerge around the time of menopause. Our data are consistent with this possibility.

Acute episodes of stress-induced SNS arousal may act as triggers for events in the context of existing cardiovascular disease. The vasomotor response of coronary arteries to stress-induced SNS activation appears to depend on whether vessels are healthy or diseased. Although healthy coronary vessels dilate, facilitating myocardial perfusion, atherosclerotic vessels constrict, leading to inadequate myocardial oxygen supply and myocardial ischemia (41). Several recent studies have shown that ischemia may be triggered by mental stress in the laboratory (42,43), as well as stress experienced during normal daily life (44). In addition to an exaggerated SNS response, blunted cardiovascular ß-AR receptor responsiveness may create a more favorable environment for the occurrence of ischemia by favoring peripheral vasoconstriction. In the PIMI study, increased peripheral vascular resistance was found to be the most reliable predictor of ischemia in response to laboratory mental stress (45). It is of note that mental stress-induced ischemia has been shown to have important prognostic clinical significance over and above exercise stress testing (46).

Hostile individuals tend to report lower levels of social support than nonhostile persons (1). This phenomenon was evident in the present study sample (R = –0.33, p < .01 between hostility and social support). We also confirmed our previously reported association of social support with CD25, whereby women who reported lower levels of perceived satisfaction with social support had reduced cardiac ß-AR responsiveness (13). The present observation that vascular ß-AR (VD40) was related to perceived social support availability also extends our previous observations for social support. Although we found in the present sample that lack of social support did not appear to account for the relationship between hostility and ß-AR blunting, hostility’s association with low social support is thought play a role in the cardiovascular risk (1,47–49). Given the substantial evidence that social isolation is linked to a variety of adverse health outcomes, including cardiovascular disease (50,51), the relationship between social support and ß-AR responsiveness may be of pathophysiological significance and merits further attention.

In conclusion, within the limitation that the present observations are cross-sectional, thereby precluding firm inferences regarding cause-effect directionality, this study provides further support that high hostility and low social support are associated with blunting of cardiovascular ß-AR responsiveness. This phenomenon is demonstrated for the first time in women, and it may be noteworthy that the study sample comprised middle-aged women, who characteristically experience a dramatic rise in cardiovascular disease risk. The present findings also demonstrate that hostility is associated with elevated daily norepinephrine excretion and are consistent with the hypothesis that the role of hostility in ß-AR blunting may be secondary to SNS hyperarousal. To the extent that ß-AR down-regulation may be an early marker of disease, the effects of hostility on cardiovascular pathophysiology may be present well in advance of its clinical manifestations.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
Supported by Grants HL 53724 from the National Institutes of Health (NIH), by M01-RR-30 General Clinical Research Centers Program, National Center for Research Resources, NIH, and by MH19109 from the National Institute of Mental Health (NIMH).

Received for publication October 24, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Smith TW. Hostility and health: current status of a psychosomatic hypothesis. Health Psychol 1992; 11: 139–50.[CrossRef][Medline]
  2. Suarez EC, Kuhn CM, Schanberg SM, Williams RB Jr, Zimmermann EA. Neuroendocrine, cardiovascular, and emotional responses of hostile men: the role of interpersonal challenge. Psychosom Med 1998; 60: 78–88.[Abstract/Free Full Text]
  3. Suls J, Wan CK. The relationship between trait hostility and cardiovascular reactivity: a quantitative review and analysis. Psychophysiology 1993; 30: 615–26.[Medline]
  4. Malarkey WB, Kiecolt-Glaser JK, Pearl D, Glaser R. Hostile behavior during marital conflict alters pituitary and adrenal hormones. Psychosom Med 1994; 56: 41–51.[Abstract/Free Full Text]
  5. Knox SS, Siegmund KD, Weidner G, Ellison RC, Adelman A, Paton C. Hostility, social support, and coronary heart disease in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Cardiol 1998; 82: 1192–96.[CrossRef][Medline]
  6. Barefoot JC, Patterson JC, Haney TL, Cayton TG, Hickman JR Jr, Williams RB. Hostility in asymptomatic men with angiographically confirmed coronary artery disease. Am J Cardiol 1994; 74: 439–42.[CrossRef][Medline]
  7. Dembroski TM, MacDougall JM, Costa PT Jr, Grandits GA. Components of hostility as predictors of sudden death and myocardial infarction in the Multiple Risk Factor Intervention Trial. Psychosom Med 1989; 51: 514–22.[Abstract/Free Full Text]
  8. Barefoot JC, Dodge KA, Peterson BL, Dahlstrom WG, Williams RB Jr. The Cook-Medley hostility scale: item content and ability to predict survival. Psychosom Med 1989; 51: 46–57.[Abstract/Free Full Text]
  9. Barefoot JC, Dahlstrom WG, Williams RB Jr. Hostility, CHD incidence, and total mortality: a 25-year follow-up study of 255 physicians. Psychosom Med 1983; 45: 59–63.[Abstract/Free Full Text]
  10. Barefoot JC, Larsen S, von der LL, Schroll M. Hostility, incidence of acute myocardial infarction, and mortality in a sample of older Danish men and women. Am J Epidemiol 1995; 142: 477–84.[Abstract/Free Full Text]
  11. Cook WW, Medley DM. Proposed hostility and Pharisaic-virtue scales for the MMPI. J Appl Psychol 1954; 38: 414–18.[CrossRef]
  12. Suarez EC, Shiller AD, Kuhn CM, Schanberg S, Williams RB Jr, Zimmermann EA. The relationship between hostility and beta-adrenergic receptor physiology in health young males. Psychosom Med 1997; 59: 481–87.[Abstract/Free Full Text]
  13. Hughes JW, Sherwood A, Blumenthal JA, Suarez EC, Hinderliter A. Hostility, social support and adrenergic receptor responsiveness among African American and white men and women. Psychosom Med 2003; 65: 582–87.[Abstract/Free Full Text]
  14. Suarez EC, Sherwood A, Hinderliter AL. Hostility and adrenergic receptor responsiveness: evidence of reduced beta-receptor responsiveness in high hostile men. J Psychosom Res 1998; 44: 261–67.[CrossRef][Medline]
  15. Wood AJ, Feldman R, Nadeau J. Physiological regulation of beta-receptors in man. Clin Exp Hypertens [A] 1982; 4: 807–17.[Medline]
  16. Mills PJ, Ziegler MG, Patterson T, Dimsdale JE, Hauger R, Irwin M, Grant I. Plasma catecholamine and lymphocyte beta 2-adrenergic receptor alterations in elderly Alzheimer caregivers under stress. Psychosom Med 1997; 59: 251–56.[Abstract/Free Full Text]
  17. Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987; 316: 1105–10.[Abstract]
  18. Smith TW, Frohm KD. What’s so unhealthy about hostility? Construct validation and psychosocial correlates of the Cook and Medley Ho Scale. Health Psychol 1985; 4: 503–20.[CrossRef][Medline]
  19. Sarason IG, Sarason BR, Shearin EN, Pierce GR. A brief measure of social support: practical and theoretical implications. J Soc Pers Relat 1987; 4: 497–510.[Abstract]
  20. Siegert RJ, Patten MD, Walkey FH. Development of a brief social support questionnaire. NZ J Psychol 1987; 16: 79–83.
  21. Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension 1989; 13: 647–55.[Abstract/Free Full Text]
  22. Sherwood A, Allen MT, Fahrenberg J, Kelsey RM, Lovallo WR, van Doornen LJ. Methodological guidelines for impedance cardiography. Psychophysiology 1990; 27: 1–23.[Medline]
  23. Cleaveland CR, Rangno RE, Shand DG. A standardized isoproterenol sensitivity test. The effects of sinus arrhythmia, atropine, and propranolol. Arch Intern Med 1972; 130: 47–52.[CrossRef][Medline]
  24. Sherwood A, Hinderliter AL. Responsiveness to alpha- and beta-adrenergic receptor agonists. Effects of race in borderline hypertensive compared to normotensive men. Am J Hypertens 1993; 6: 630–635.[Medline]
  25. Kotchen TA, Guthrie GP, McKean H, Kotchen JM. Adrenergic responsiveness in prehypertensive subjects. Circulation 1982; 65: 285–90.[Abstract/Free Full Text]
  26. James GD, Sealey JE, Alderman M, Ljungman S, Mueller FB, Pecker MS, Laragh JH. A longitudinal study of urinary creatinine and creatinine clearance in normal subjects. Race, sex, and age differences. Am J Hypertens 1988; 1: 124–31.[Medline]
  27. Tsujimoto G, Manger WM, Hoffman BB. Desensitization of beta-adrenergic receptors by pheochromocytoma. Endocrinology 1984; 114: 1272–78.[Abstract]
  28. Wallukat G. The beta-adrenergic receptors. Herz 2002; 27: 683–90.[CrossRef][Medline]
  29. Bertel O, Buhler FR, Kiowski W, Lutold BE. Decreased beta-adrenoreceptor responsiveness as related to age, blood pressure, and plasma catecholamines in patients with essential hypertension. Hypertension 1980; 2: 130–138.[Abstract]
  30. Feldman RD. Beta-adrenergic receptor alterations in hypertension—physiological and molecular correlates. Can J Physiol Pharmacol 1987; 65: 1666–72.[Medline]
  31. Stein CM, Nelson R, Deegan R, He H, Wood M, Wood AJ. Forearm beta adrenergic receptor-mediated vasodilation is impaired, without alteration of forearm norepinephrine spillover, in borderline hypertension. J Clin Invest 1995; 96: 579–85.
  32. Dhalla NS, Dixon IM, Rupp H, Barwinsky J. Experimental congestive heart failure due to myocardial infarction: sarcolemmal receptors and cation transporters. Basic Res Cardiol. 1991; 86: suppl 23.
  33. Brodde OE. Beta-adrenoceptors in cardiac disease. Pharmacol Ther 1993; 60: 405–30.[CrossRef][Medline]
  34. Calls J, Cases A, Lario S, Esforzado N, Pare JC, Azqueta M, Jimenez W, Rivera-Fillat F. Beta-adrenergic receptor density and function in left ventricular hypertrophy in young essential hypertensives. J Hum Hypertens 2000; 14: 17–21.[CrossRef][Medline]
  35. Gilbert EM, Olsen SL, Renlund DG, Bristow MR. Beta-adrenergic receptor regulation and left ventricular function in idiopathic dilated cardiomyopathy. Am J Cardiol 1993; 71: 23C–9C.[CrossRef][Medline]
  36. Xiao RP, Tomhave ED, Wang DJ, Ji X, Boluyt MO, Cheng H, Lakatta EG, Koch WJ. Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases. J Clin Invest 1998; 101: 1273–82.[Medline]
  37. Konstam MA. Improving clinical outcomes with drug treatment in heart failure: what have trials taught? [Review] [20 refs]. Am J Cardiol 2003; 91: 9–14D.
  38. Maggioni AP, Sinagra G, Opasich C, Geraci E, Gorini M, Gronda E, Lucci D, Tognoni G, Balli E, Tavazzi L. Beta blockers in patients with congestive heart failure: guided use in clinical practice investigators. Treatment of chronic heart failure with beta adrenergic blockade beyond controlled clinical trials: the BRING-UP experience. Heart Br Cardiac Soc 2003; 89: 299–305.
  39. Suls J, Wan CK, Costa PT Jr. Relationship of trait anger to resting blood pressure: a meta-analysis. Health Psychol 1995; 14: 444–56.[CrossRef][Medline]
  40. Messinger-Rapport BJ, Thacker HL. Prevention for the older woman. A practical guide to managing cardiovascular disease. Geriatrics 2002; 57: 22–26.
  41. Krantz DS, Kop WJ, Santiago HT, Gottdiener JS. Mental stress as a trigger of myocardial ischemia and infarction. Cardiol Clin 1996; 14: 271–87.[Medline]
  42. Rozanski A, Bairey CN, Krantz DS, Friedman J, Resser KJ, Morell M, Hilton-Chalfen S, Hestrin L, Bietendorf J, Berman DS. Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease. N Engl J Med 1988; 318: 1005–12.[Abstract]
  43. Blumenthal JA, Jiang W, Waugh RA, Frid DJ, Morris JJ, Coleman RE, Hanson M, Babyak M, Thyrum ET, Krantz DS. Mental stress-induced ischemia in the laboratory and ambulatory ischemia during daily life. Association and hemodynamic features. Circulation 1995; 92: 2102–8.[Abstract/Free Full Text]
  44. Gullette EC, Blumenthal JA, Babyak M, Jiang W, Waugh RA, Frid DJ, O’Connor CM, Morris JJ, Krantz DS. Effects of mental stress on myocardial ischemia during daily life [comment]. JAMA 1997; 277: 1521–26.[Abstract]
  45. Goldberg AD, Becker LC, Bonsall R, Cohen JD, Ketterer MW, Kaufman PG, Krantz DS, Light KC, McMahon RP, Noreuil T, Pepine CJ, Raczynski J, Stone PH, Strother D, Taylor H, Sheps DS. Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI). Circulation 1996; 94: 2402–9.[Abstract/Free Full Text]
  46. Sheps DS, McMahon RP, Becker L, Carney RM, Freedland KE, Cohen JD, Sheffield D, Goldberg AD, Ketterer MW, Pepine CJ, Raczynski JM, Light K, Krantz DS, Stone PH, Knatterud GL, Kaufmann PG. Mental stress-induced ischemia and all-cause mortality in patients with coronary artery disease: Results from the Psychophysiological Investigations of Myocardial Ischemia study [comment]. Circulation 2002; 105: 1780–4.[Abstract/Free Full Text]
  47. Williams RB. Basic biological mechanisms. In: Siegman AW, Smith TW, editors. Anger, hostility, and the heart. Hillsdale, NJ: Lawrence Erlbaum; 1994: 117–25.
  48. Smith TW. Concepts and methods in the study of anger, hostility, and health. In: Siegman AW, Smith TW, editors. Anger, hostility, and the heart. Hillsdale, NJ: Lawrence Erlbaum; 1994: 23–42.
  49. Gallo LC, Smith TW. Patterns of hostility and social support: Conceptualizing psychosocial risk factors as characteristics of the person and the environment. J Res Pers 1999; 33: 281–310.
  50. Kawachi I, Colditz GA, Ascherio A, Rimm EB, Giovannucci E, Stampfer MJ, Willett WC. A prospective study of social networks in relation to total mortality and cardiovascular disease in men in the USA. J Epidemiol Commun Health 1996; 50: 245–51.[Abstract]
  51. Orth-Gomer K, Rosengren A, Wilhelmsen L. Lack of social support and incidence of coronary heart disease in middle-aged Swedish men. Psychosom Med 1993; 55: 37–43.[Abstract/Free Full Text]




This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sherwood, A.
Right arrow Articles by Hinderliter, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sherwood, A.
Right arrow Articles by Hinderliter, A. L.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS