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.
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.


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), beta-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, beta-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.
Winkler
Karl
K
Department of Medicine, University of Freiburg, Freiburg, Germany. kwinkler@ukl.uni-freiburg.de
Winkelmann
Bernhard R
BR
Scharnagl
Hubert
H
Hoffmann
Michael M
MM
Grawitz
Andrea Busse
AB
Nauck
Markus
M
Böhm
Bernhard O
BO
März
Winfried
W
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000201:enzymology; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000201:enzymology; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000201:enzymology; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology; D054467:Phospholipases A2; D011859:Radiography; D012307:Risk Factors
D015415:Biomarkers; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase