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Plasminogen Activator Inhibitor-1 Is Associated with Impaired Endothelial Function in Women with Systemic Lupus Erythematosus
aUniversity of Michigan, aDivision of Rheumatology, cDivision of Cardiology, Ann Arbor, Michigan 48109, USA bLondon School of Hygiene & Tropical Medicine, Infectious Disease Epidemiology Unit, London WC1E 7HT, UK
Address for correspondence: Emily C. Somers, University of Michigan Health System, Division of Rheumatology, 1150 W. Medical Center Dr., 5520 MSRB 1, Ann Arbor, MI 48109-0680. Voice: 734-936-1166; fax: 734-763-4151. emsomers{at}umich.edu
Endothelial function, measured noninvasively by brachial artery flow-mediated dilatation (FMD), has been shown to be impaired in patients with systemic lupus erythematosus (SLE). We hypothesized that depressed FMD in SLE patients is associated with increased levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis and regulator of vasoactivity. In this cross-sectional study of female SLE patients under the age of 55, putative markers of cardiovascular disease (CVD) such as PAI-1 were measured in addition to lupus-related disease activity (SLEDAI). The primary outcome, FMD, was measured using high-resolution ultrasound of the brachial artery gated to the R wave to determine endothelial-dependent vasomotion. Endothelial-independent vasomotion was measured in response to nitroglycerin (NMD). Seventy-six female SLE patients, mean age 38.3 ± 9.4 years, were included. All patients demonstrated normal NMD responses, indicating that depression of FMD was related to decreased endothelial nitric oxide production. Increased PAI-1 was related to depressed FMD by univariate regression (P = 0.004). In a multivariable regression model adjusting for t-PA (tissue plasminogen activator)/PAI-1 ratio, SLEDAI, age at visit, family history of cardiovascular disease, SLE disease duration and body mass index, every 1 ng/mL increase in PAI-1 was associated with a reduction of 0.07 units FMD (P = 0.039). PAI-1 was associated with impaired endothelial dysfunction, after controlling for several potential confounders. Given the high incidence of cardiovascular disease in SLE, further investigation of the role of subclinical markers of CVD is needed.
Key Words: systemic lupus erythematosus (SLE) • plasminogen activator inhibitor-1 (PAI-1) • endothelium • flow-mediated dilatation
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