Platelet-Activating Factor Acetylhydrolase Activity Indicates Angiographic Coronary Artery Disease Independently of Systemic Inflammation and Other Risk Factors

Abstract

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 (rϭ0.517), apolipoprotein B (rϭ0.644), and non-HDL cholesterol (rϭ0.648) 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 (Ϫ12%; PϽ0.001), aspirin (Ϫ6%; PϽ0.001), ␤-blockers (Ϫ6%; PϽ0.001), and digitalis (ϩ7%; PϽ0.001). 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, ␤-blocker, and digitalis, the odds ratio for CAD associated with increasing PAF-AH activity was 1.39 (95% CI 1.26 to 1.54, PϽ0.001), 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. (Circulation. 2005;111:980-987.)

Association of Lipoprotein-associated Phospholipase A2 with Coronary Calcification among American and Japanese Men

“…However, this mutation has not been found among Caucasians. 8 Among Caucasians, Lp-PLA2 was reported to be an independent risk factor for CAD and stroke in many, [9][10][11][12][13][14] but not all, studies. [15][16][17] Data assessing the relationship of CAC with Lp-PLA2 are very limited among Caucasians 18,19 and there are no data, to our knowledge, among the Japanese.…”

“…[9][10][11][12][13][14] Whether Lp-PLA2 is an independent predictor of CAC or not is less clear. Only two studies examined the association between coronary calcification and Lp-PLA2 levels among white populations with inconsistent findings.…”

Higher lipoprotein-associated phospholipase A2 levels are associated with coronary atherosclerosis documented by coronary angiography

“…28,29 The results of our multivariate analysis revealed that higher Lp-PLA2 levels were as powerful a predictor of coronary atherosclerosis as either LDL-C or HbA 1c . Thus, we postulate that the presence of atherosclerotic plaque could be evaluated by measuring circulating Lp-PLA2 concentrations.…”

Lp-PLA2: A New Kid on the Block

“…An important issue is to determine whether to measure the mass of Lp-PLA 2 or to measure its enzyme activity. Several of the epidemiology studies measured only Lp-PLA 2 mass (2-5; 7-9; 15,16 ), whereas others measured only enzyme activity, (6,10,11,14 ) and a few have measured both in the same study population (12,13 ). The relatively low correlation (r ϭ 0.36) between Lp-PLA 2 mass and activity in recent studies has raised the question of precisely what is being measured with the respective assays (12 ).…”

“…These efforts have focused on 3 broad classes of biomarkers: (a) vascular imaging to identify the presence of atheroma or its composition; (b), functional assessments that reflect abnormal arterial homeostasis (e.g., arterial stiffness); and (c), measurements of soluble biomarkers. In recent years, several epidemiology studies have revealed an association between lipoprotein-associated phospholipase A 2 (Lp-PLA 2 )-a biomarker that may be viewed as a potential link between noxious effects of oxidized LDL cholesterol and elusive plaque vulnerability-and cardiovascular events (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Lp-PLA 2 , a member of phospholipase A 2 superfamily, is produced by inflammatory cells of myeloid origin, is associated with circulating atherogenic lipoproteins, and is highly expressed in the diseased vessel ( Fig.…”