Journal of Clinical Lipidology
Volume 3, Issue 2 , Pages 85-93 , April 2009

The role of lipoprotein-associated phospholipase A2 on cardiovascular disease risk assessment and plaque rupture: a clinical review

  • Kota J. Reddy, MD

      Affiliations

    • Reddy Cardiac Wellness, 3519 Town Center Blvd, Sugar Land, TX 77479 USA
    • ,
  • Manmeet Singh, MD

      Affiliations

    • Reddy Cardiac Wellness, 3519 Town Center Blvd, Sugar Land, TX 77479 USA
    • Corresponding Author InformationCorresponding author.
    • ,
  • Joey R. Bangit, MD

      Affiliations

    • Reddy Cardiac Wellness, 3519 Town Center Blvd, Sugar Land, TX 77479 USA
    • ,
  • Richard R. Batsell, PhD

      Affiliations

    • Rice University, Houston, TX USA

Received 14 January 2009 ,Accepted 17 January 2009.

References 

  1. Atkinson AJ, Colburn WA, Degruttola VG. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Therapeut. 2001;69:89–95
  2. Casas JP, Shah T, Cooper J, et al. Insight into the nature of the CRP-coronary event association using Mendelian randomization. Int J Epidemiol. 2006;35:922–931
  3. Davey Smith G, Lawlor DA, Harbord R, et al. Association of C-reactive protein with blood pressure and hypertension: life course confounding and mendelian randomization tests of causality. Arterioscler Thromb Vasc Biol. 2005;25:1051–1056Erratum, 2005; 25:e129
  4. Ridker PM, Danielson E, Fonseca FA, et al. JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–2207
  5. Kinlay S. Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. J Am Coll Cardiol. 2007;49:2003–2009
  6. Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol. 2005;46:1855–1862
  7. Danesh J, Kaptoge S, Mann AG, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med. 2008;5:e78
  8. Swedberg K, Cleland J, Dargie H, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary update 2005. Rev Esp Cardiol. 2005;58:1062–1092
  9. De Sutter J, De Bacquer D, Cuypers S, et al. Plasma N-terminal pro-brain natriuretic peptide concentration predicts coronary events in men at work: a report from the BELSTRESS study. Eur Heart J. 2005;26:2644–2649
  10. Kistorp C, Raymond I, Pedersen F, et al. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA. 2005;293:1609–1616
  11. Olsen MH, Hansen TW, Christensen MK, et al. N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population. Eur Heart J. 2007;28:1374–1381
  12. Sarwar N, Sattar N, Gudnason V, Danesh J. Circulating concentrations of insulin markers and coronary heart disease: a quantitative review of 19 Western prospective studies. Eur Heart J. 2007;28:2491–2497
  13. Sattar N, Wannamethee G, Sarwar N, et al. Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation. 2006;114:623–629
  14. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004;291:1730–1737
  15. Dada N, Kim NW, Wolfert RL. Lp-PLA2: an emerging biomarker of coronary heart disease. Expert Rev Mol Diagn. 2002;2:17–22
  16. Häkkinen T, Luoma JS, Hiltunen MO, et al. Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 1999;19:2909–2917
  17. Kolodgie FD, Burke AP, Taye A, et al. Lp-PLA2 is highly expressed in macrophages of coronary lesions prone to rupture. Presented at the Annual Scientific Session of the American Heart Association. New Orleans, LA, November 11, 2004.
  18. MacPhee CH, Moores KE, Boyd HF, 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. Biochem J. 1999;338:479–487
  19. 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;82:159–165
  20. Tsimikas S, Willeit J, Knoflach M, et al. Lipoprotein-associated phospholipase A2 activity, ferritin levels, metabolic syndrome, and 10-year cardiovascular and non-cardiovascular mortality: results from the Bruneck study. Eur Heart J. 2009;30:107–115
  21. Packard CJ, O'Reilly DS, Caslake MJ, 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;343:1148–1155
  22. Koenig W, Khuseyinova N, Löwel 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;110:1903–1908
  23. Caslake MJ, Packard CJ, Suckling KE, Holmes SD, Chamberlain P, Macphee CH. Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis. 2000;150:413–419
  24. Brilakis ES, Joseph P, McConnell JP, et al. Higher levels of lipoprotein-associated phospholipase A2 are associated with higher incidence of cardiovascular events at follow up independent of C-reactive protein. Eur Heart J. 2004;26:137–144
  25. Ballantyne CM, Hoogeveen RC, Bang H, 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;165:2479–2484
  26. Oei H-HS, Van der Meer IM, Hofman A, et al. Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study. Circulation. 2005;166:2073–2080
  27. 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;166:2073–2080
  28. Robins SJ, Collins D, Nelson JJ, Bloomfield HE, Asztalos BF. Lipoprotein-associated phospholipase A2, predicts cardiovascular events in the low HDL-C and low LDL-C population of Veterans Affairs HDL Intervention Trial (VA-HIT). Presented at European Society of Cardiology World Congress of Cardiology. Barcelona: Spain; September 2006;Abstract 3448
  29. Wassertheil-Smoller S, Kooperberg C, McGinn AP, et al. Lipoprotein-associated phospholipase A2 and risk of ischemic stroke in postmenopausal women: The Women's Health Initiative Observational Study. Circulation. 2007;115:657–e222
  30. Wassertheil-Smoller S, Kooperberg C, McGinn AP, et al. Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women. Hypertension. 2008;51:1115–1122
  31. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657–671
  32. Kolodgie FD, Burke AP, Skorija KS, et al. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2006;26:2523–2529
  33. Wolfert RL, Kim NW, Selby RG, Sarno MJ, Warnick RG, Sudhir K. Biological variability and specificity of lipoprotein-associated phospholipase A2 (Lp-PLA2), a novel marker of cardiovascular risk. Circulation. 2004;110:309
  34. Serruys PW, Héctor M, García-García HM, et al. Effects of the direct lipoprotein-associated phospholipase A2 inhibitor darapladib on human coronary atherosclerotic plaque. Circulation. 2008;118:1171–1182
  35. Mohler ER, Ballantyne CM, Davidson MH, et al. Darapladib Investigators. 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. J Am Coll Cardiol. 2008;51:1642–1644
  36. Zhao XQ, Yuan C, Hatsukami TS, et al. Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study. Arterioscler Thromb Vasc Biol. 2001;21:1623–1629
  37. Winkler K, Abletshauser C, Friedrich I, Hoffmann MM, Wieland H, März W. Fluvastatin slow-release lowers platelet-activating factor acetyl hydrolase activity: a placebo-controlled trial in patients with type 2 diabetes. J Clin Endocrinol Metab. 2004;89:1153–1159
  38. O'Donoghue M, Morrow DA, Sabatine MS, 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;113:1745–1752
  39. Albert MA, Glynn RJ, Wolfert RL, Ridker PM. The effect of statin therapy on lipoprotein associated phospholipase A2 levels. Atherosclerosis. 2005;182:193–198
  40. Muhlestein JB, May HT, Jensen JR. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol. 2006;48:396–401
  41. Saougos VG, Tambaki AP, Kalogirou M, et al. Differential effect of hypolipidemic drugs on lipoprotein-associated phospholipase A2. Arterioscler Thromb Vasc Biol. 2007;27:2236–2243
  42. Kuvin JT, Dave DM, Sliney KA, et al. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease. Am J Cardiol. 2006;98:743–745
  43. Reddy R, Bangit J, Zaheer M, et al. Lipoprotein-associated phospholipase A2 mass is significantly reduced in dyslipidemic patients treated with lifestyle counseling and combination lipid modifying drug therapy. Orlando, FL: Presented at Scientific Sessions of the American Heart Association; 2007;
  44. Karabina SA, Liapikos TA, Grekas G, Goudevenos J, Tselepis AD. Distribution of PAF-acetylhydrolase activity in human plasma low-density lipoprotein subfractions. Biochim Biophys Acta. 1994;1213:34–38
  45. Marathe GK, Zimmerman GA, McIntyre TM. Platelet-activating factor acetylhydrolase, and not paraoxonase-1, is the oxidized phospholipid hydrolase of high density lipoprotein particles. J Biol Chem. 2003;278:3937–3947
  46. Guerra CT, Caini P, Giannini C, et al. Effect of chronic hepatitis C virus infection on inflammatory lipid mediators. Dig Liver Dis. 2007;39(suppl 1):S76–S82
  47. Caini P, Guerra CT, Giannini C, et al. Modifications of plasma platelet-activating factor (PAF)-acetylhydrolase/PAF system activity in patients with chronic hepatitis C virus infection. J Viral Hepat. 2007;14:22–28

PII: S1933-2874(09)00025-7

doi: 10.1016/j.jacl.2009.01.004

Journal of Clinical Lipidology
Volume 3, Issue 2 , Pages 85-93 , April 2009

Article Tools

* Image Usage & Resolution