Lipoprotein-Associated Phospholipase A 2 Bound on High-Density Lipoprotein Is Associated With Lower Risk for Cardiac Death in Stable Coronary Artery Disease Patients

Results Follow-up data were obtained from 477 patients. One hundred twenty-three patients (25.8%) presented with cardiovascular events (24 cardiac deaths, 47 acute coronary syndromes, 28 revascularizations, 22 arrhythmic events, and 2 strokes). Total plasma Lp-PLA2 mass and activity were predictors of cardiac death (hazard ratio [HR]: 1.013; 95% confidence interval [CI]: 1.005 to 1.021; p 0.002; and HR: 1.040; 95% CI: 1.005 to 1.076; p 0.025, respectively) after adjustment for traditional risk factors for CAD. In contrast, HDLLp-PLA2 mass and activity were associated with lower risk for cardiac death (HR: 0.972; 95% CI: 0.952 to 0.993; p 0.010; and HR: 0.689; 95% CI: 0.496 to 0.957; p 0.026, respectively) after adjustment for traditional risk factors for CAD.

[1]  M. Rizzo,et al.  Therapeutic modulation of lipoprotein-associated phospholipase A2 (Lp-PLA2). , 2011, Current pharmaceutical design.

[2]  E. Braunwald,et al.  Study design and rationale for the Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial in patients after an acute coronary syndrome. , 2011, American heart journal.

[3]  I. T. Silva,et al.  Antioxidant and inflammatory aspects of lipoprotein-associated phospholipase A2 (Lp-PLA2 ): a review , 2011, Lipids in Health and Disease.

[4]  C. Held,et al.  Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease. , 2010, American heart journal.

[5]  J. Danesh,et al.  Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies , 2010, The Lancet.

[6]  J. Willerson,et al.  Lipoprotein-associated phospholipase A2 as a novel risk marker for cardiovascular disease: a systematic review of the literature. , 2010, Texas Heart Institute journal.

[7]  A. Tselepis,et al.  The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. , 2009, Biochimica et biophysica acta.

[8]  Qingbo Xu,et al.  Lipoprotein-associated phospholipase A2 activity, ferritin levels, metabolic syndrome, and 10-year cardiovascular and non-cardiovascular mortality: results from the Bruneck study. , 2008, European heart journal.

[9]  Frits Mastik,et al.  Effects of the Direct Lipoprotein-Associated Phospholipase A2 Inhibitor Darapladib on Human Coronary Atherosclerotic Plaque , 2008, Circulation.

[10]  M. Topham,et al.  Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein* , 2008, Journal of Biological Chemistry.

[11]  Jeffrey L. Anderson.  Lipoprotein-associated phospholipase A2: an independent predictor of coronary artery disease events in primary and secondary prevention. , 2008, The American journal of cardiology.

[12]  M. Corson,et al.  Review of the evidence for the clinical utility of lipoprotein-associated phospholipase A2 as a cardiovascular risk marker. , 2008, The American journal of cardiology.

[13]  M. Hanefeld,et al.  The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. , 2008, Journal of the American College of Cardiology.

[14]  M. Elisaf,et al.  Alterations in the High Density Lipoprotein Phenotype and HDL-Associated Enzymes in Subjects with Metabolic Syndrome , 2008, Lipids.

[15]  S. Solomon,et al.  Prognostic Utility of Lipoprotein-Associated Phospholipase A2 for Cardiovascular Outcomes in Patients With Stable Coronary Artery Disease , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[16]  R. Wolfert,et al.  Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2 , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[17]  S. Miura,et al.  Ratio of LDL- to HDL-associated platelet-activating factor acetylhydrolase may be a marker of inflammation in patients with paroxysmal atrial fibrillation. , 2007, Circulation journal : official journal of the Japanese Circulation Society.

[18]  Christodoulos Stefanadis,et al.  Dietary patterns: a Mediterranean diet score and its relation to clinical and biological markers of cardiovascular disease risk. , 2006, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[19]  R. Virmani,et al.  Lipoprotein-Associated Phospholipase A2 Protein Expression in the Natural Progression of Human Coronary Atherosclerosis , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[20]  A. Moss,et al.  High lipoprotein-associated phospholipase A2 is a risk factor for recurrent coronary events in postinfarction patients. , 2006, Clinical chemistry.

[21]  H. Brenner,et al.  Lipoprotein-Associated Phospholipase A2 Predicts Future Cardiovascular Events in Patients With Coronary Heart Disease Independently of Traditional Risk Factors, Markers of Inflammation, Renal Function, and Hemodynamic Stress , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[22]  William Stewart,et al.  Recommendations for chamber quantification. , 2006, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[23]  M. Elisaf,et al.  Lipoprotein-associated phospholipase A2 activity is a marker of small, dense LDL particles in human plasma. , 2005, Clinical chemistry.

[24]  Y. Sasaguri,et al.  Local Expression of Platelet-Activating Factor-Acetylhydrolase Reduces Accumulation of Oxidized Lipoproteins and Inhibits Inflammation, Shear Stress-Induced Thrombosis, and Neointima Formation in Balloon-Injured Carotid Arteries in Nonhyperlipidemic Rabbits , 2005, Circulation.

[25]  M. Elisaf,et al.  Lipoprotein-associated PAF-acetylhydrolase activity in subjects with the metabolic syndrome. , 2005, Prostaglandins, leukotrienes, and essential fatty acids.

[26]  S. Ylä-Herttuala,et al.  Intravascular adenovirus-mediated lipoprotein-associated phospholipase A2 gene transfer reduces neointima formation in balloon-denuded rabbit aorta. , 2005, Atherosclerosis.

[27]  W. März,et al.  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 , 2005, Circulation.

[28]  C. Ballantyne,et al.  PLAC™ test for identification of individuals at increased risk for coronary heart disease , 2005, Expert review of molecular diagnostics.

[29]  E. Brilakis,et al.  Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up. , 2005, European heart journal.

[30]  B. Ainsworth,et al.  International physical activity questionnaire: 12-country reliability and validity. , 2003, Medicine and science in sports and exercise.

[31]  F. Cambien,et al.  Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis. , 2003, Journal of lipid research.

[32]  M. Elisaf,et al.  Fenofibrate induces HDL-associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins Published, JLR Papers in Press, March 1, 2003. DOI 10.1194/jlr.M200452-JLR200 , 2003, Journal of Lipid Research.

[33]  A. Tselepis,et al.  Inflammation, bioactive lipids and atherosclerosis: potential roles of a lipoprotein-associated phospholipase A2, platelet activating factor-acetylhydrolase. , 2002, Atherosclerosis. Supplements.

[34]  J. Goudevenos,et al.  Altered distribution of platelet-activating factor- acetylhydrolase activity between LDL and HDL as a function of the severity of hypercholesterolemia. , 2002, Journal of lipid research.

[35]  J. Goudevenos,et al.  Atorvastatin Preferentially Reduces LDL-Associated Platelet-Activating Factor Acetylhydrolase Activity in Dyslipidemias of Type IIA and Type IIB , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[36]  D. Stengel,et al.  Prevents Injury-induced Neointima Formation and Reduces Spontaneous Atherosclerosis in Acetylhydrolase − Adenovirus-mediated Gene Transfer of Human Platelet-activating Factor Adenovirus-mediated Gene Transfer of Human Platelet-activating Factor–acetylhydrolase Prevents Injury-induced Neointima Forma , 2022 .

[37]  D. Shih,et al.  HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[38]  D. Stengel,et al.  HDLassociated PAF‐AH reduces endothelial adhesiveness in apoE−/− mice , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[39]  Yasuo Ikeda,et al.  Cellular source(s) of platelet-activating-factor acetylhydrolase activity in plasma. , 1999, Biochemical and biophysical research communications.

[40]  D. Tew,et al.  Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor. , 1999, The Biochemical journal.

[41]  E. Ninio,et al.  PAF-degrading acetylhydrolase is preferentially associated with dense LDL and VHDL-1 in human plasma. Catalytic characteristics and relation to the monocyte-derived enzyme. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[42]  D. Stafforini,et al.  Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor. , 1987, The Journal of biological chemistry.