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Background- Platelet- activating factor acetylhydrolase(PAFAH), 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), β - 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, β - 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.