Regulation of Hemostasis by the Sympathetic Nervous System: Any Contribution to Coronary Artery Disease?

Abstract

Within the last two decades, hemostasis factors have emerged as ‘new’ risk factors for coronary artery disease. Historical studies on the physiology of the sympathetic nervous system (SNS) attributed accelerated blood clotting to the components of the fight-flight response. Although this has not been demonstrated, exaggerated clotting related to SNS hyperactivity might confer an increased arterial thrombotic risk. This review outlines the effects of sympathetic activation as mimicked by adrenergic infusions and as elicited by mental stress and physical exercise, and the molecular mechanisms involved. A selective review of the pertinent literature was undertaken. Sympathetic activation provokes a simultaneous increase in molecules of both the coagulation and fibrinolysis pathways within minutes, resulting in net hypercoagulability as a part of normal human physiology. Catecholamines and adrenergic receptors interact to mediate hemostatic changes. Exaggerated procoagulant changes in individuals with a preexistent atherosclerotic disease, in those experiencing ongoing stressful life circumstances and in the physically untrained might confer a thrombotic threat with sympathetic activation. Initial evidence suggests that nonselective β-adrenergic blockade may attenuate clotting acceleration upon SNS activation. Prospective studies are needed to demonstrate whether exaggerated clotting as elicited by the SNS is associated with an increased risk of cardiovascular morbidity and mortality. If confirmed, intervention studies targeted at reducing this risk, for example with drugs, psychotherapy (including stress management) and regular physical exercise, would be warranted.

Chronic stress impacts the cardiovascular system: animal models and clinical outcomes

“…Another explanation for a heightened coagulatory status could be sympathetic nervous system activation (266). There is a solid body of evidence that support this notion.…”

Anticipatory Cognitive Stress Appraisal and the Acute Procoagulant Stress Response in Men

“…The thickening of blood in response to an acute and potentially life-threatening stressor is therefore physiological, because it provided our ancestors with an evolutionary benefit (2). Under certain circumstances, however, a procoagulant stress response may incur harm for the cardiovascular system because hypercoagulability could contribute to overt thrombosis (4). For instance, individuals with preexisting atherosclerotic diseases exhibit exaggerated hypercoagulability in response to acute stress (5)(6)(7)(8).…”

“…For instance, individuals with preexisting atherosclerotic diseases exhibit exaggerated hypercoagulability in response to acute stress (5)(6)(7)(8). If, in patients with coronary artery disease (CAD), a stress-induced blood pressure peak provokes rupture of a vulnerable atherosclerotic plaque (9), a hypercoagulable milieu could accelerate intracoronary thrombus growth and critical vessel occlusion (4). Therefore, a better insight into factors that might exaggerate the procoagulant stress response to an extent that may become harmful for certain populations could have clinical value.…”

Procoagulant State in Heart Failure With Preserved Left Ventricular Ejection Fraction

“…[15][16][17][18][19][20][21][22] Activation of the sympathetic and renin-angiotensin-aldosterone systems provokes a simultaneous increase in molecules of both the coagulation and fibrinolysis pathways within minutes, resulting in net hypercoagulability. [23][24][25] Since neurohormonal, inflammatory, and endothelial changes are disrupted in heart failure regardless of the type of ventricular impairment (systolic or diastolic), an increase in haemostatic markers is expected in heart failure regardless of whether the underlying left ventricular failure is systolic or isolated diastolic in origin.…”