HOSTILITY, CORONARY RISK, AND {alpha}-ADRENERGIC TO {beta}-ADRENERGIC RECEPTOR DENSITY RATIO * Response

doi:10.1097/01.psy.0000117562.61101.9d

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LETTERS TO THE EDITOR

HOSTILITY, CORONARY RISK, AND ${alpha}$ -ADRENERGIC TO ß-ADRENERGIC RECEPTOR DENSITY RATIO

Jeffrey P. Kahn, MD

Weill Medical College, Cornell University, New York, New York

Hughes et al. (1) have published a wonderful study of the correlationbetween hostility and social support on the one hand, with invivo ${alpha}$ -adrenergic and ß-adrenergic receptor responsivenesson the other. One of the most interesting applications of thesefindings is to the spasm-injury theory of coronary artery atherogenesis.For example, ${alpha}$ -receptor stimulation produces coronary vasoconstriction,while ß-receptor stimulation produces coronary vasodilatation.By that theory, chronic adrenergically mediated vasospasticactivity should lead to a relative decrease in ${alpha}$ -adrenergic receptordensity, and to a relative increase in ß-adrenergicreceptor density. Previous research has reported that measuresof hostility and Type A behavior are associated in vitro withdecreased ${alpha}$ ₂-adrenergic receptor density on platelets, and withincreased ß₂-adrenergic receptor density on lymphocytes(2, 3). More importantly, the ${alpha}$ ₂/ß₂ receptor densityratio is a more refined physiological indicator model of recentvasoconstrictive activation, and is highly correlated with angertrait and Type A behavior in subjects with a family historyof early coronary artery disease (2). It would be interestingto see the data by Hughes et al. (1) for a similar subgroup,and especially whether their in vivo data show a similar correlationof an ${alpha}$ /ß-receptor responsiveness ratio with measuresof hostility and social support.

REFERENCES

Hughes JW, Sherwood A, Blumenthal JA, Suarez EC, Hinderliter AL. Hostility, social support, and adrenergic receptor responsiveness among African-American and white men and women. Psychsom Med 2003; 65: 582–7.[Abstract/Free Full Text]
Kahn JP, Perumal AS, Gully RJ, Smith TM, Cooper TB, Klein DF. Correlation of Type A behaviour with adrenergic receptor density: implications for coronary artery disease pathogenesis. Lancet 1987; 8565: 1937–9,ii.
Mills PJ, Shiller AD, Kuhn CM, Schanberg S, Williams RB, Zimmerman EA. The relationship between hostility and beta-adrenergic receptor physiology in healthy young males. Psychsom Med 1997; 59: 481–7.[Abstract/Free Full Text]

Response

Andrew Sherwood, PhD, Joel W. Hughes, PhD, James A. Blumenthal, PhD, Edward C. Suarez, PhD and Alan L. Hinderliter, MD

Duke University Medical Center, Durham, North Carolina

We agree that one important implication of studies relatingpsychosocial characteristics to abnormal adrenergic receptorfunction is the potential impact on coronary vasomotor regulation.As might be expected from the independent relationships thatwe observed between hostility scores and our in vivo ${alpha}$ ₁-adrenergic(r = -.15, p = .07) and ß-adrenergic (r = .25, p <.01) receptor responsiveness indices, the ${alpha}$ ₁/ß ratiodid indeed exhibit a significant negative correlation with hostility(r = -0.20, p < .05). We assessed family history of coronaryheart disease (CHD) by asking subjects to indicate whether,to their knowledge, neither (N = 113), one (N = 34), or both(N = 2) parents had been diagnosed with CHD. Although familyhistory of CHD was not found to moderate the relationship betweenhostility/social support and adrenergic receptor function, subjectswith a positive family history (one or both parents) exhibitedheightened ${alpha}$ ₁-adrenergic receptor responsiveness compared withsubjects with a negative family history (PD25: FH+ = 233 µgphenylephrine; FH- = 314 µg phenylephrine; p = .005 adjustedfor gender, ethnicity, and blood pressure). In contrast, therewere no differences associated with family history of CHD forß-adrenergic receptor responsiveness (CD25: FH+ =2.11 µg isoproterenol; FH- = 2.11 µg isoproterenol;p = .98), and the ${alpha}$ ₁/ß ratio also was not significantlydifferent (p = .1). These observations are consistent with thenotion that downregulation of ß-adrenergic receptorsassociated with hostility may be of particular pathophysiologicsignificance in the context of ${alpha}$ -adrenergic receptor hyperresponsiveness.Such an adrenergic receptor imbalance may favor ${alpha}$ ₁-adrenergicallymediated vasoconstriction, which in the coronary vessels hasbeen associated with the potential to trigger myocardial ischemia(1). Interestingly, ß-adrenergically mediated vasodilationappears to be mediated in part via vascular endothelial nitricoxide release (2) and therefore is dependent on endothelialhealth, which is characteristically poor in patients with CHD.The relationship among hostility, social support, and ß-adrenergicreceptor regulation that we observed suggests a plausible pathophysiologicpathway that may provide important insights into how these psychosocialtraits may act as risk factors for CHD. However, the inabilityto establish cause-effect relationships remains a major limitationof the existing cross-sectional studies, and prospective studiesare needed that would allow the natural history of the interrelationshipsbetween psychosocial characteristics, adrenergic receptor function,and the clinical manifestation of CHD to be more fully understood.