Markedly impaired fibrinolytic balance contributes to cardiovascular risk in adults with growth hormone deficiency.
BACKGROUND
Adults with GH deficiency (GHD) have multiple cardiovascular risk factors, including an unfavorable lipid profile and body composition as well as impairments in endothelial function and cardiac performance. We hypothesized that GHD is associated with elevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of plasminogen activation in the circulation.


OBJECTIVE
The objective of the study was to determine the fibrinolytic profile of adults with GHD in comparison with controls.


METHODS
This was a prospective, observational study including 12 adults with GHD. Twelve gender-, age-, and body mass index-matched adults served as controls.


METHODS
The primary outcome measures were circadian plasma PAI-1 antigen with corresponding tissue-plasminogen activator (tPA) activity values. Endothelial function was assessed by flow-mediated vasodilation and fibrinolytic potential by venous occlusion test.


RESULTS
Adults with GHD exhibited an unfavorable 24-h fibrinolytic profile characterized by a mean 62% elevation in PAI-1 antigen (2.77 ng/ml after adjustment for baseline PAI-1; P = 0.049) in the setting of a mean 24% reduction in tPA activity (-0.17 IU/ml after adjustment for baseline tPA; P = 0.003). Fibrinolytic response was defective in GHD, as demonstrated by a sustained elevation in PAI-1 activity greater than 4 IU/ml after venous occlusion [7.2 IU/ml (interquartile range 0.8-17.4); P = 0.018]. Endothelial function was impaired in GHD, as quantified by percent flow-mediated vasodilation over 120 sec [area under the curve 3.8 (interquartile range -2.4 to 7.9) vs. 12.8 (interquartile range 2.1-19.4); P = 0.043].


CONCLUSIONS
Adults with GHD demonstrate alterations in plasma fibrinolytic balance, including elevated levels of PAI-1 antigen with decreased tPA activity. These changes may contribute to the increased cardiovascular morbidity within this population.
Devin
Jessica K
JK
Divisions of Endocrinology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. JKS98@Alum.Dartmouth.org
Blevins
Lewis S
LS
Verity
Denise K
DK
Chen
Qingxia
Q
Bloodworth
John R
JR
Covington
Joseph
J
Vaughan
Douglas E
DE
D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology*; D016022:Case-Control Studies; D002940:Circadian Rhythm; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D006130:Growth Disorders / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D013006:Growth Hormone / Q000172:deficiency*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D005337:Fibrin; D013006:Growth Hormone; D010959:Tissue Plasminogen Activator