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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:106.)
© 2006 American Heart Association, Inc.

Vascular Biology

Lipoprotein-Associated Phospholipase A₂ Is an Independent Marker for Coronary Endothelial Dysfunction in Humans

Eric H. Yang; Joseph P. McConnell; Ryan J. Lennon; Gregory W. Barsness; Geralyn Pumper; Stacy J. Hartman; Charanjit S. Rihal; Lilach O. Lerman; Amir Lerman

From the Division of Cardiovascular Diseases (E.H.Y., G.W.B., G.P., C.S.R., A.L.), Department of Laboratory Medicine and Pathology (J.P.M., S.J.H.), Division of Biostatistics (R.J.L.), and Division of Nephrology and Hypertension (L.O.L.), Mayo College of Medicine, Rochester, Minn.

Correspondence to Amir Lerman, MD, Division of Cardiovascular Disease and Internal Medicine, Mayo College of Medicine, 200 First St SW, Rochester, MN 55905. E-mail lerman.amir{at}mayo.edu

Objective— The purpose of the current study was to determine whether lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans.

Methods and Results— Patients (172) with no significant coronary artery disease (<30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA₂ were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow (63.8±73.2 and 32.0±71.7 versus 78.4±73.2%; P<0.001) and greater epicardial coronary artery vasoconstriction (–14.1±14.7 and –23.3±25.1 versus –9.5±15.2% mean diameter change; P<0.001) in response to acetylcholine. Patients with coronary endothelial dysfunction had significantly higher serum concentrations of Lp-PLA₂ than those with normal endothelial function (246.2±71.6 versus 209±56.7 ng/mL; P=0.001). The odds ratio for coronary endothelial dysfunction in patients with Lp-PLA₂ in the highest tertile was 3.3 (95% CI, 1.6 to 6.6).

Conclusions— Lp-PLA₂ is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans.

Coronary endothelial dysfunction can be considered a marker for early atherosclerosis and has been shown to be associated with an increased risk of ischemic cardiac events and stroke. The results of the current study show that Lp-PLA₂, an enzyme involved in the metabolism of oxidized phospholipids, is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans.

Key Words: lipoprotein-associated phospholipase A₂ • endothelial function • inflammatory markers

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Lipoprotein-Associated Phospholipase A₂ and Cardiovascular Risk: State of the Evidence and Future Directions

Carlos Iribarren
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