Published online before print February 14, 2005, doi: 10.1161/01.CIR.0000156457.35971.C8
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(Circulation. 2005;111:980-987.)
© 2005 American Heart Association, Inc.
Epidemiology |
Platelet-Activating Factor Acetylhydrolase Activity Indicates Angiographic Coronary Artery Disease Independently of Systemic Inflammation and Other Risk Factors
The Ludwigshafen Risk and Cardiovascular Health Study
From the Department of Medicine, University of Freiburg, Freiburg, Germany (K.W., M.M.H., A.B.G., M.N.); Cardiology Group Frankfurt-Sachsenhausen, Frankfurt, Germany (B.R.W.); Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Graz, Graz, Austria (H.S., W.M.); and Division of Endocrinology and Diabetes, Department of Medicine, University of Ulm, Ulm, Germany (B.O.B.).
Reprint requests to Karl Winkler, MD, Department of Medicine, Hugstetter Straße 55, D-79106 Freiburg, Germany. E-mail kwinkler{at}ukl.uni-freiburg.de
Received April 1, 2004; revision received November 20, 2004; accepted November 23, 2004.
Background— Platelet-activating factor acetylhydrolase (PAF-AH), also denoted as lipoprotein-associated phospholipase A2, is a lipoprotein-bound enzyme that is possibly involved in inflammation and atherosclerosis. This study investigates the relationship of PAF-AH activity to angiographic coronary artery disease (CAD), the use of cardiovascular drugs, and other established risk factors.
Methods and Results— PAF-AH activity, lipoproteins, sensitive C-reactive protein (sCRP), fibrinogen, serum amyloid A, and white blood cell count were determined in 2454 subjects with angiographically confirmed CAD and in 694 control subjects. PAF-AH activity was highly correlated with LDL cholesterol (r=0.517), apolipoprotein B (r=0.644), and non-HDL cholesterol (r=0.648) but not with sCRP or fibrinogen. PAF-AH activity was lower in women than in men and was affected by the intake of lipid-lowering drugs (–12%; P<0.001), aspirin (–6%; P<0.001), ß-blockers (–6%; P<0.001), and digitalis (+7%; P<0.001). Unlike sCRP, fibrinogen, and serum amyloid A, PAF-AH activity was not elevated in unstable angina, non–ST-elevation myocardial infarction, or ST-elevation myocardial infarction. When nonusers of lipid-lowering drugs were examined, PAF-AH activity was associated with the severity of CAD and the number of coronary vessels with significant stenoses. In individuals not taking lipid-lowering drugs and after adjustment for use of aspirin, ß-blocker, and digitalis, the odds ratio for CAD associated with increasing PAF-AH activity was 1.39 (95% CI 1.26 to 1.54, P<0.001), a finding that was robust against further adjustments.
Conclusions— PAF-AH activity is not an indicator of the systemic inflammation that accompanies acute coronary syndromes. PAF-AH activity is affected by a number of cardiovascular drugs; however, after such medication use was accounted for, PAF-AH activity was associated with angiographic CAD, complementary to sCRP and independently of established risk factors such as LDL cholesterol.
Key Words: lipoproteins • C-reactive protein • cholesterol
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