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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 1/2009

01-02-2009

Lipoprotein-Associated and Secretory Phospholipase A2 in Cardiovascular Disease: The Epidemiological Evidence

Authors: Wolfgang Koenig, Natalie Khuseyinova

Published in: Cardiovascular Drugs and Therapy | Issue 1/2009

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Abstract

Introduction

Among other lipid related biomarkers, lipoprotein-associated phospholipase A2 (Lp-PLA2) and type II secretory phospholipase A2 (sPLA2) represent emerging candidates for refined assessment of future cardiovascular disease (CVD) risk. Indeed, emerging evidence from more than prospective 15 studies conducted since 2000, clearly demonstrate the prognostic ability of increased Lp-PLA2 concentrations or elevated activity for risk of future coronary heart disease (CHD) and stroke. Moreover, Lp-PLA2 might have similar predictive power for both, incident CHD in initially healthy subjects, as well as for recurrent events in those with clinically manifest atherosclerosis.

Discussion

By contrast, to date, there are only few prospective studies that have investigated the relationship of sPLA2 with future CVD risk. However, most of them show a positive association between increased mass or elevated activity and future atherosclerotic complications. Nonetheless, since inhibitors of Lp-PLA2 and sPLA2 have already been developed, these enzymes may be considered as novel therapeutic targets to treat residual risk in certain high risk patient groups.

Conclusion

This review summarizes the epidemiologic evidence on the association between increased mass or elevated activity of these two phospholipases and risk of CVD.
Literature
1.
Stafforini DM. Biology of lipoprotein-associated phospholipase A2. Cardiovasc Drugs Ther. 2008;in press.
2.
Corson MA, Jones PH, Davidson MH. Review of the evidence for the clinical utility of lipoprotein-associated phospholipase A2 as a cardiovascular risk marker. Am J Cardiol 2008;101:S41–50.CrossRef
3.
Packard CJ, O’Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med 2000;343:1148–55.PubMedCrossRef
4.
Blake GJ, Dada N, Fox JC, Manson JE, Ridker PM. A prospective evaluation of lipoprotein-associated phospholipase A2 levels and the risk of future cardiovascular events in women. J Am Coll Cardiol 2001;38:1302–6.PubMedCrossRef
5.
Ballantyne CM, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Heiss G, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation 2004;109:837–42.PubMedCrossRef
6.
Koenig W, Khuseyinova N, Lowel H, Trischler G, Meisinger C. Lipoprotein-associated phospholipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population: results from the 14-year follow-up of a large cohort from southern Germany. Circulation 2004;110:1903–8.PubMedCrossRef
7.
Oei HH, van der Meer IM, Hofman A, Koudstaal PJ, Stijnen T, Breteler MMB, et al. Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study. Circulation 2005;111:570–5.PubMedCrossRef
8.
Kiechl S, Willeit J, Mayr M, Viehweider B, Oberhollenzer M, Kronenberg F, et al. Oxidized phospholipids, lipoprotein(a), lipoprotein-associated phospholipase A2 activity, and 10-year cardiovascular outcomes: prospective results from the Bruneck study. Arterioscler Thromb Vasc Biol 2007;27:1788–95.PubMedCrossRef
9.
Daniels LB, Laughlin GA, Sarno MJ, Bettencourt R, Wolfert RL, Barrett-Connor E. Lipoprotein-associated phospholipase A2 is an independent predictor of incident coronary heart disease in an apparently healthy older population: the Rancho Bernardo Study. J Am Coll Cardiol 2008;51:913–9.PubMedCrossRef
10.
Jenny NS, Solomon C, Cushman M, Nelson JJ, Tracy RP, Psaty BM, et al. Lipoprotein-associated phospholipase A2 and cardiovascular disease: results from the Cardiovascular Health Study. Circulation 2006;113:E–332. Abstract.
11.
Caslake MJ, Cooney J, Murray E, Bedford D, Robertson M, Nelson JJ, et al. Lipoprotein-associated phospholipase A2 as a risk factor for coronary vascular disease in the elderly. Atheroscler Suppl 2006;7:484. Abstract.CrossRef
12.
O’Donoghue M, Morrow DA, Sabatine MS, Murphy SA, McCabe CH, Cannon CP, et al. 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 2006;113:1745–52.PubMedCrossRef
13.
Oldgren J, James SK, Siegbahn A, Wallentin L. Lipoprotein-associated phospholipase A2 does not predict mortality or new ischaemic events in acute coronary syndrome patients. Eur Heart J 2007;28:699–704.PubMedCrossRef
14.
Gerber Y, McConnell JP, Jaffe AS, Weston SA, Killian JM, Roger VL. Lipoprotein-associated phospholipase A2 and prognosis after myocardial infarction in the community. Arterioscler Thromb Vasc Biol 2006;26:2517–22.PubMedCrossRef
15.
Möckel M, Müller R, Vollert JO, Müller C, Danne O, Gareis R, et al. Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach: the North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II). Clin Res Cardiol 2007;96:604–12.PubMedCrossRef
16.
Brilakis ES, McConnell JP, Lennon RJ, Elesber AA, Meyer JG, Berger PB. Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up. Eur Heart J 2004;26:137–44.PubMedCrossRef
17.
Koenig W, Twardella D, Brenner H, Rothenbacher D. 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. Arterioscler Thromb Vasc Biol 2006;26:1586–93.PubMedCrossRef
18.
Corsetti JP, Rainwater DL, Moss AJ, Zareba W, Sparks CE. High lipoprotein-associated phospholipase A2 is a risk factor for recurrent coronary events in postinfarction patients. Clin Chem 2006;52:1331–8.PubMedCrossRef
19.
Sabatine MS, Morrow DA, O’Donoghue M, Jablonksi KA, Rice MM, Solomon S, et al. PEACE Investigators. Prognostic utility of lipoprotein-associated phospholipase A2 for cardiovascular outcomes in patients with stable coronary artery disease. Arterioscler Thromb Vasc Biol 2007;27:2463–9.PubMedCrossRef
20.
Winkler K, Hoffmann MM, Winkelmann BR, Friedrich I, Schäfer G, Seelhorst U, et al. Lipoprotein-associated phospholipase A2 predicts 5-year cardiac mortality independently of established risk factors and adds prognostic information in patients with low and medium high-sensitivity C-reactive protein (the Ludwigshafen risk and cardiovascular health study). Clin Chem 2007;53:1440–7.PubMedCrossRef
21.
Ballantyne CM, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Chambless LE, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Arch Intern Med 2005;165:2479–84.PubMedCrossRef
22.
Wassertheil-Smoller S, Kooperberg C, McGinn AP, Kaplan RC, Hsia J, Hendrix SL, et al. Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women. Hypertension 2008;51:1115–22.PubMedCrossRef
23.
Elkind MS, Tai W, Coates K, Paik MC, Sacco RL. High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med 2006;166:2073–80.PubMedCrossRef
24.
Garza CA, Montori VM, McConnell JP, Somers VK, Kullo IJ, Lopez-Jimenez F. Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review. Mayo Clin Proc 2007;82:159–65.PubMedCrossRef
25.
The Lp-PLA2 Studies Collaboration. 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.CrossRef
26.
Hurt-Camejo E, Camejo G, Peilot H, Oörni K, Kovanen P. Phospholipase A(2) in vascular disease. Circ Res 2001;89:298–304.PubMedCrossRef
27.
Jaross W, Eckey R, Menschikowski M. Biological effects of secretory phospholipase A(2) group IIA on lipoproteins and in atherogenesis. Eur J Clin Invest 2002;32:383–93.PubMedCrossRef
28.
Peilot H, Rosengren B, Bondjers G, Hurt-Camejo E. Interferon-gamma induces secretory group IIA phospholipase A2 in human arterial smooth muscle cells. Involvement of cell differentiation, STAT-3 activation, and modulation by other cytokines. J Biol Chem 2000;275:22895–904.PubMedCrossRef
29.
Anthonsen MW, Stengel D, Hourton D, Ninio E, Johansen B. Mildly oxidized LDL induces expression of group IIa secretory phospholipase A(2) in human monocyte-derived macrophages. Arterioscler Thromb Vasc Biol 2000;20:1276–82.PubMed
30.
Webb N. Biology of secretory phospholipase A2. Cardiovasc Drugs Ther. 2008; in press.
31.
Kugiyama K, Ota Y, Takazoe K, Moriyama Y, Kawano H, Miyao Y, et al. Circulating levels of secretory type II phospholipase A2 predict coronary events in patients with coronary artery disease. Circulation 1999;100:1280–4.PubMed
32.
Kugiyama K, Ota Y, Sugiyama S, Kawano H, Doi H, Soejima H, et al. Prognostic value of plasma levels of secretory type II phospholipase A2 in patients with unstable angina pectoris. Am J Cardiol 2000;86:718–22.PubMedCrossRef
33.
Liu PY, Li YH, Tsai WC, Chao TH, Tsai LM, Wu HL, Chen JH. Prognostic value and the changes of plasma levels of secretory type II phospholipase A2 in patients with coronary artery disease undergoing percutaneous coronary intervention. Eur Heart J 2003;24:1824–32.PubMedCrossRef
34.
Mallat Z, Steg PG, Benessiano J, Tanguy ML, Fox KA, Collet JP, et al. Circulating secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes. J Am Coll Cardiol 2005;46:1249–57.PubMedCrossRef
35.
Koenig W, Vossen CY, Mallat Z, Brenner H, Tedgui A, Rothenbacher D. Association between type II secretory phospholipase A2 plasma concentrations and activity and cardiovascular events in patients with coronary heart disease. Eur Heart J. 2008;28. Abstract Supplement.
36.
Boekholdt SM, Keller TT, Wareham NJ, Luben R, Bingham SA, Day NE, et al. Serum levels of type II secretory phospholipase A2 and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study. Arterioscler Thromb Vasc Biol 2005;25:839–46.PubMedCrossRef
37.
Mallat Z, Benessiano J, Simon T, Ederhy S, Sebella-Arguelles C, Cohen A, et al. Circulating secretory phospholipase A2 activity and risk of incident coronary events in healthy men and women. The EPIC-NORFOLK Study. Arterioscler Thromb Vasc Biol 2007;27:1177–83.PubMedCrossRef
38.
Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation 2007;115:949–52.PubMedCrossRef
39.
Rosenson RS. Emerging therapies that reduce phospholipase activity and implications for atherogenesis. Cardiovasc Drugs Ther. 2008;in press.
Metadata
Title
Lipoprotein-Associated and Secretory Phospholipase A2 in Cardiovascular Disease: The Epidemiological Evidence
Authors
Wolfgang Koenig
Natalie Khuseyinova
Publication date
01-02-2009
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 1/2009
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-008-6135-6

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