Clinical Investigations: Acute Ischemic Heart Disease
Effect of β2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress*,**,

https://doi.org/10.1067/mhj.2002.123146Get rights and content

Abstract

Background Procoagulant stress responses may contribute to atherosclerosis development and acute coronary thrombosis. In the present study, we examined the role of β2-adrenergic receptor function and plasma catecholamines in the stress-induced increase in the 2 hypercoagulability markers thrombin-antithrombin III (TAT) complex and fibrin D-dimer (DD). Methods Lymphocyte β2-adrenoreceptor sensitivity and density were assessed at rest, and plasma levels of TAT, DD, epinephrine, and norepinephrine were measured at rest and in response to a standardized mental stress task in 19 normotensive and mildly hypertensive nonmedicated subjects (mean age 38 years, age range 29 to 48 years). Results The stressor elicited a significant increase in TAT (P =.024), DD (P =.026), and norepinephrine (P =.005). Resting β2-adrenoreceptor sensitivity (isoproterenol-stimulated cyclic adenosine monophosphate production) plus the norepinephrine change scores (stress minus rest) accounted for 59% of the variance in the absolute TAT increase in response to stress (P =.001). Hypertension status and demographic variables such as sex did not influence the results. Conclusions Acute mental stress may trigger a hypercoagulable state evidenced by increased thrombin activity and increased fibrin turnover. β2-Adrenergic receptor sensitivity and plasma catecholamine activity may mediate the procoagulant response to acute stressors. These mechanisms may help explain the adverse impact of mental stress on the cardiovascular system. (Am Heart J 2002;144:68-72.)

Section snippets

Subjects and study design

The subjects consisted of 19 (13 normotensive and 6 mildly hypertensive) volunteers recruited from the San Diego community through advertisement or word-of-mouth referral to participate in a study on the effects of the SNS on cardiovascular physiology. Subjects gave written consent for the study protocol, which was approved by the University of California San Diego Human Subjects Committee in accordance with institutional guidelines. Subjects took no medications and were excluded if they had

Results

As shown in Figures 1 and 2, mental stress led to a significant increase in TAT (P =.024), DD (P =.026), and norepinephrine (P =.005); there was a trend for epinephrine to increase (P =.072).

. Log10 normalized mean ± SE of hypercoagulability markers. Both thrombin-antithrombin III (TAT) (pmol/L) and D-dimer (ng/mL) significantly increased (asterisk, P <.05) in response to combined 9-minute speech and mirror star tracing task.

. Mean ± SE norepinephrine values (pg/mL) and the log10 normalized mean ±

Discussion

The physiologic mechanisms by which increased sympathoadrenal activation stimulates hemostasis are not fully understood. Others have found a positive association between increased plasma epinephrine levels and fibrinolytic capacity12 and an inverse relation between plasma epinephrine and antithrombin III.13 In addition, adrenergic receptor blockade studies suggest that the β2-receptor is responsible for increased procoagulant activities of factor VIII and of von Willebrand factor on the one

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    *

    Supported by grants HL36005, HL44915, and RR00827 from the National Institutes of Health, fellowship 81BE-56155 from the Swiss National Science Foundation, and an educational grant from Novartis Foundation, Switzerland.

    **

    Reprint requests: Joel E. Dimsdale, MD, Department of Psychiatry, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0804.

    E-mail: [email protected]

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