Lp-PLA2 (Lipoprotein-associated phospholipase A2) – also known as platelet-activating factor acetylhydrolase (PAF-AH) – is a vascular-specifc inflammatory enzyme, predominantly expressed by macrophages, lymphocytes and foam cells in atherosclerotic plaques. Circulating Lp-PLA2 is mainly associated with apolipoprotein B-containing lipoproteins, hence closely associated with low-density lipoprotein (LDL). The enzyme hydrolyzes oxidized phospholipids on LDL particles within the arterial intima, generating two highly inflammatory mediators, lysophosphatidylcholine (Lyso-PC) and oxidized non-esterified fatty acids (oxNEFAs).
Many important studies confirm a strong association between Lp-PLA2 levels and cardiovascular risk among different populations. These studies show that in individuals with normal LDL, elevated Lp-PLA2 levels were strongly associated with heart disease and ischemic stroke, independent of traditional risk markers and high-sensitive CRP. Due to the fact that Lp-PLA2 is involved in the causal pathway of plaque inflammation and plaque rupture, the testing for Lp-PLA2 represents a valuable adjunctive tool which goes beyond traditional cardiovascular risk assessment.
The Importance of Lp-PLA2 Testing
It is well known, that inflammatory processes play an important role in the pathogenesis of atherosclerosis. Established risk factors account for part of the cardiovascular diseases only. Lp-PLA2, a new reliable marker in the atherosclerotic risk assessment, is able to close this diagnostic gap.
Studies provide strong evidence, that the presence of Lp-PLA2 is associated with an increased risk of cardiac death, myocardial infarction, acute coronary syndrome and ischemic stroke. Increased Lp-PLA2 concentrations can be found in vulnerable atherosclerotic plaques and allow discrimination between morphologically identical stable and unstable plaques. Lp-PLA2 testing is an excellent complement to angiography because it detects very small plaques not visible by medical imaging. Unlike traditional atherosclerotic risk markers Lp-PLA2 is highly specifc for vascular inflammation, has low biological variability, and plays a causative role in atherosclerotic plaque inflammation.
Caslake MJ et al 2000. Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis:150(2): 413-419.
Stafforini DM et al 1999. Molecular basis of the interaction between plasma platelet-activating factor acetylhydrolase and low density lipoprotein. J Biol Chem;274:7018-24.
Wilensky RL et al 2008. Inhibition of Lipoprotein-associated phospholipase A2 reduces complexcoronary atherosclerotic plaque development. Nat Med;14:1059-66.
Vickers KC et al 2009. Relationship of Lipoprotein-Associated Phospholipase A2 and Oxidited Low-Density Lipoprotein in Carotid Atherosclerosis. JLR;50(9):1735-44.
Zalewski A and Macphee C 2005. Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol;25:923-31.
Caslake MJ and Packard CJ 2003. Lipoprotein-Associated Phospholipase A2 (platelet-activating factor acetylhydrolase) and cardiovascular disease. Curr Opin Lipidol;14:347-52.
Packard CJ et al 2000. Lipoprotein-Associated Phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med;343:1148-55.
Garza CA et al 2007. Lipoprotein-Associated Phospholipase A2 and cardiovascular disease: a systemic review. Association between Mayo Clin Proc;82:159-65.
Kaminsky LA and Ozmek C 2012.Diurnal variation in lipoprotein-associated phospholipase A2 (Lp-PLA2). Clin Biochem;45(9):700-702.
Atherosclerotic Plaques and Lp-PLA2
Kolodgie FD et al 2006. Lipoprotein-Associated Phospholipase A2 expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol;26:2523-29.
Mannheim D et al 2008. Enhanced expression of Lp-PLA2 and lysophosphatidylcholine in symptomatic carotid atherosclerotic plaques.
Frank D et al 2006. Lipoprotein-Associated Phospholipase A2 Protein Expression in the Natural Progression of Human Coronary Atherosclerosis. Arterioscler Thromb Vasc Biol;26:2523-2529.
The Lp-PLA2 Studies Collaboration: Lipoprotein-Associated Phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 2010;375:1536-44. Biol;27:1788-1795.
The Lp-PLA2 Studies Colaboration. Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases. Eur J Cardiovasc Prev Rehabil 2007;14:3-11.
Caslake MJ et al. 2010. Lipoprotein-associated phospholipase A2, inflammatory biomarkers, and risk of cardiovascular disease in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Atherosclerosis;210(1):28-34.
Kiechl S et al 2007. Oxidized Phospholipids, Lipoprotein(a), Lipoprotein-Associated Phospholipase A2 Activity, and 10-Year Cardiovascular Outcomes: Prospective Results From the Bruneck Study. Arterioscler Thromb Vasc Biol;27:1788-1795.
Moeckel M et al. 2007 – The North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II). Lipoprotein-associated phopolipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach. Clin Res Cardiol 96:1-9.
Lp-PLA2 – Mass vs Activity
Persson M et al 2007. Elevated Lp-PLA2 Levels Add Prognostic Information of the Metabolic Syndrome on Incidence of Cardiovascular Events Among Middle-Aged Nondiabteic Subjects. Arterioscler Thromb Vasc Biol;27:1411-1416.
O’Donoghue M et al 2006. Lipoprotein-associated phospholipase A2 and its association with cardiovascular outcomes in patients with acute coronary syndromes in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial. Circulation;113(14):1745-52.
Lee KK et al 2011. Racial variation in lipoprotein-associated phospholipase A2 in older adults. BMC Cardiovascular Disorders;11:38.
Brilakis ES et al 2008. Influence of Race and Sex on Lipoprotein-Associated Phospholipase A2 Levels: Observations from the Dallas Heart Study. Atherosclerosis;199(1):110-115.
Hoffmann MM et al 2009. Genetic variants and haplotypes of Lipoprotein-associated phospholipase A2 and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascukar Helath Study). J Thromb Haemost;7:41-48.
Therapeutic Action Studies – Effects on Lp-PLA2
Muhlestein JB et al 2006. The Reduction of Inflammatory Biomarkers by Statin, Fibrate, and Combination Therapy Among Diabetic Patients With Mixed Dyslipidemia. J Am CollCardiol;48:396-401.
Winkler K et al 2004. Fluvastatin Slow-Release Lowers Platelet-Activating Factor Acetyl Hydrolase Activity: A Placebo-Controlled Trial in Patients with Type 2 Diabetes. J Clin Endocrinol Metab;89:1153-1159.
Albert MA et al 2005. The Effectof Statin Therapy on Lipoprotein Associated Phospholipase A2 Levels. Atherosclerosis;182:193-198.
Schaefer EJ et al 2005. Effects of Atorvastatin Versus Other Statins on Fasting and Postprandial C-Reactive Protein and Lipoprotein-Associated Phospholipase A2 in Patients With CoronaryHeart Disease Versus Control Subjects. Am J Cardiol;95:1025-1032.
Vasilios G et al 2007. Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2. Arterioscler Throm Vasc Biol;27:2236-2243.
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