Enter search term


Accurate detection. Reliable prediction. Patient stratification.

Valuable novel cardiovascular risk assessment tools to help you better manage CVD patients


sPLA2-IIA (AccuCardia™ ELISA Test System):

Cardiovascular disease (CVD) accounts for nearly half of noncommunicable diseases worldwide, and is a leading cause of mortality.1, 2 At least 35% of individuals that suffer from a myocardial infarction have previously survived one.5 The severe clinical consequences of CVD are typically caused by atherosclerotic lesions, which are formed when connective tissue elements, inflammatory cells, lipids, and debris build up in the artery wall.6-8

Despite existing treatment options and growing awareness, by the year 2020 cardiovascular disease is projected to be the main cause of death worldwide.9 This highlights the urgent need for improved CVD diagnostic tools to determine an individual's cardiovascular risk. Because of the key role they play in atherosclerotic CVD, phospholipase A2 (PLA2) enzymes have emerged as promising diagnostic targets to assist in better risk stratification.10-13

PLA2 enzymes are a family of proteins that catalyze the hydrolysis of phospholipids at the sn-2 position, yielding pro-inflammatory lysophospholipids and fatty acids.14-16 Secreted PLA2 (sPLA2) proteins make up a subgroup of this family, and consist of 10 calcium-dependent extracellular enzymes with relatively low molecular masses.9 A member of this subgroup, sPLA2-IIA, has been the focus of over 20 published research and clinical studies aimed at investigating its role in, and association with, cardiovascular conditions such as coronary artery disease (CAD) and atherosclerosis.9, 11 For example, immunohistochemical studies show that sPLA2-IIA is present in normal arteries, and that its extracellular distribution and level of cell expression is increased in early and late atherosclerotic lesions, suggesting that the enzyme may play a causal role in atherogenesis.17, 18

In fact, sPLA2-IIA has a well-established role in inflammation, and research has revealed an important link between sPLA2-IIA activity and atherosclerotic processes.12,13 Additional studies have demonstrated that overexpression of human group sPLA2-IIA is related to atherosclerotic lesion development,11 and other studies suggest that sPLA2-IIA may be an important factor in initiation, progression, and/or rupture of atherosclerotic plaque.10

Several reports have linked increased plasma levels of sPLA2-IIA with recurrent events and adverse outcomes in patients with stable CAD.19, 20 Recently, additional studies have also shown that increased levels of sPLA2-IIA indicate an increased risk of recurrent cardiac events and death in patients presenting with acute coronary syndromes such as MI and unstable angina.21, 22

Gamma-Prime Fibrinogen (GammaCoeur™ CVD Risk ELISA Test System):

Fibrinogen is a heterogeneous mixture of isoforms with varying relative proportions.30 Alternative mRNA processing and posttranslational modifications give rise to several different fibrinogen isoforms with widely varying characteristics. In addition, because fibrinogen is a 6-chain molecule containing 2 copies each of the Aα, Bβ, and γ chains, various combinations of altered chains can be assembled, particularly in fibrinogens resulting from heterozygous polymorphisms or mutations. The fibrinogen γ chain has 2 isoforms, the gamma A (γA or simply γ) isoform and the gamma-prime (or γB) isoform.31-32 The gamma-prime isoform arises from alternative mRNA processing which results in the substitution of the carboxyl terminal 4 amino acids with a different 20-amino acid sequence. The gamma-prime chain is usually paired with the more common γA chain.33-34

Gamma-prime fibrinogen typically constitutes approximately 10% of total fibrinogen in plasma. Gamma-prime fibrinogen has several biochemical and biophysical properties that distinguish it from the more common γA isoform. Clots made from fibrinogen containing gamma-prime chains in the presence of factor XIII are highly resistant to fibrinolysis.35 In addition, the gamma-prime chain contains a binding site for thrombin, and clots made from gamma-prime fibrinogen have been reported to have an altered clot architecture.36-37

Possibly as a result of these properties, recent studies suggest that gamma-prime fibrinogen is a risk factor for cardiovascular disease.38-44 An association has been found between gamma-prime fibrinogen concentrations and prevalent coronary artery disease, myocardial infarction, stroke, and inflammation. 38-44

The significance of sPLA2 in cardiovascular event prevention has been demonstrated in numerous studies:

  • EPIC-Norfolk study with asymptomatic patients (primary prevention)23, 24
  • FAST-MI study with acute coronary events patients (secondary prevention)25, 26
  • GRACE study with acute CAD patients (secondary prevention)27
  • KAROLA study with CHD patients (secondary prevention)20
  • MIRACL study with UA or AMI patients (secondary prevention)21
  • PEACE study with stable CHD patients (secondary prevention)28
  • PIVUS study with elderly patients (primary prevention)29

The significance of Gamma Prime Fibrinogen in cardiovascular event prevention has been demonstrated in numerous studies:

  • Lovely et. al study (primary prevention)42-43
  • PAVE study (primary prevention)44
  • Penn. State University CAD Study (primary prevention)33
  • STOCKHOLM CA Risk Factor Study (primary prevention)40
  • ARIC study for atherosclerotic risk (primary prevention)45

The AccuCardia™ ELISA test system quantifies sPLA2-IIA, which has been statistically proven to be independently associated with CVD-enabling clinicians to risk-stratify CVD patients and apply appropriate therapeutic regimes

  • sPLA2-IIA levels are associated with atherosclerotic processes
  • Elevated levels indicate 3x increased odds of ACS (GRACE) and AMI (MIRACL)
  • Measurement of sPLA2-IIA is an accurate predictor of all-cause mortality

The GammaCoeur™ CVD Risk ELISA test system quantifies γ ‘ Fibrinogen, independently associated with CVD, enabling clinicians to risk-stratify CVD patients and apply appropriate therapeutic regimes

  • γ ‘ Fibrinogen levels determine fibrinolysis resistance in clots
  • Elevated levels indicate 3x increased odds of heart attack (FRAMINGHAM & PAVE)
  • Elevated levels indicate 7x increased odds of CAD (Lovely)


  1. Laslett LJ, Alagona P Jr, Clark BA 3rd, Drozda JP Jr, Saldivar F, et al. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol. 2012;60:S1-S49.
  2. World Health Organization. Fact sheet N°317, http://www.who.int/mediacentre/factsheets/fs317/en/ (accessed July 2014).
  3. World Health Organization. Global status report on noncommunicable diseases 2010. Geneva, 2011.
  4. World Health Organization. Global atlas on cardiovascular disease prevention and control. Geneva, 2011.
  5. Million Hearts: About Disease and Stroke Fact Sheet. http://millionhearts.hhs.gov/abouthds/cost-consequences.html (accessed July 2015).
  6. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1658-1695.
  7. Hademenous GJ, Massoud TF. Biophysical mechanisms of stroke. Stroke. 1997;28:2067-2077.
  8. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995;92:1355-1374.
  9. American Heart Association. A Public Health Action Plan to Prevent Heart Disease and Stroke. http://www.cdc.gov/dhdsp/action_plan/pdfs/action_plan_full.pdf (accessed July 2015).
  10. Lambeau G, Gelb MH. Biochemistry and physiology of mammalian secreted phospholipases A2. Annu Rev Biochem. 2008;77:495-520.
  11. Mallat Z, Lambeau G, Tedgui A. Lipoprotein-associated and secreted phospholipases A2 in cardiovascular disease: Roles as biological effectors and biomarkers. Circulation. 2010;122:2183-2200.
  12. Karabina SA, Gora S, Atout R, Ninio E. Extracellular phospholipases in atherosclerosis. Biochimie. 2010;92:594-600.
  13. Rosenson RS, Hurt-Camejo E. Phospholipase A2 enzymes and the risk of atherosclerosis. Eur Heart J. 2012;33:2899-2909.
  14. Balsinde J, Balboa MA, Insel PA, Dennis EA. Regulation and Inhibition of phospholipase A2. Annu Rev Pharmacol Toxicol. 1999;39:175-189.
  15. Kudo I, Murakami M. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 2002; 68-69:3-58.
  16. Schaloske RH, Dennis EA. The phospholipase A2 superfamily and its group numbering system. Biochim Biophys Acta. 2006;1761:1246-1259.
  17. Ivandic B, Castellini LW, Wang X-P, Qiao J-H, Mehrabian M, Navab M, Fogelman AM, Grass DS, Swanson ME, Beer MCD, Beer FD, Lusis AJ. Role of group II secretory phospholipase A2 in atherosclerosis. 1. Increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIA phospholipase A2. Arterioscler Thromb Vasc Biol. 1999;19:1284-1290.
  18. Hurt-Camejo, E., Sartipy, P., Peilot, H., Rosengren, B., Wiklund, O., & Camejo, G. (2003). Phospholipase A2 in the pathogenesis of cardiovascular disease. Membrane Lipid Signaling in Aging and Age-Related Disease, 12, 177.
  19. Kugiyama K, Ota Y, Takazoe K, Moriyama Y, Kawano H, et al. Circulating levels of secretory type II phospholipase A(2) predict coronary events in patients with coronary artery disease. Circulation. 1999;100:1280-1284.
  20. Koenig W, Vossen CY, Ziad M, Brenner H, Benessiano J, 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. 2009;30:2742-2748.
  21. Ryu SK, Mallat Z, Benessiano J, Tedgui A, Olsson AG, et al. Phospholipase A2 enzymes, high-dose atovastatin, and prediction of ischemic events after acute coronary syndromes. Circulation. 2012;125:757-766, 2012.
  22. Xin H, Chen ZY, Lv XB, Liu S, Lian ZX, et al. Serum secretory phospholipase A2-IIA (sPLA2-IIA) levels in patients surviving acute mycardial infarction. Eur Rev Med Pharmacol Sci. 2013;17:999-1004.
  23. Mallat Z, Benessiano J, Simon T, Ederhy S, Sebella-Arguelles C, Cohen A, Huart V, Wareham NJ, Luben R, Khaw KT, Tedgui A, Boekholdt SM. 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(5):1177-1183.
  24. Tsimikas S, Mallat Z, Talmud PJ, Kastelein JJP, Wareham NJ, Sandhu MS, Miller ER, Benessiano J, Tedgui A, Witztum JL, Khaw KT, Boekholdt SM. Oxidation-specific biomarkers, Lipoprotein(a) and risk of fatal and nonfatal coronary events. JACC. 2010;56(12):946-955.
  25. Simon T et al., European Society of Cardiology Meeting, 2008, p. 1317.
  26. Simon T et al., European Society of Cardiology Meeting, 2008, p. 5109.
  27. Mallat Z, Steg G, Benessiano J, Tanguy ML, Fox KA, Collet JP, Dabbous OH, Henry P, Carruthers KF, Dauphin A, Arguelles CS, Masliah J, Hugel B, Montalescot G, Freyssinet JM, Asselain B, and Tedgui A. Circulating secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes. J Am Coll Cardiol. 2005;46(7):1249-1257.
  28. O’Donoghue ML, Mallat Z, Morrow DA, Benessiano J, Sloan S, Omland T, Solomon SF, Braunwald E, Tedgui A, Sabatine MS. Prognostic utility of secretory phospholipase A2 in patients with stable coronary artery disease. Clinical Chemistry. 2011;57(9):1311-1317.
  29. Lind L, Simon T, Johansson L, Kotti S, Hansen T, Machecourt J, Ninio E, Tedgui A, Danchin N, Ahlstrom H, Mallat Z. Circulating levels of secretory- and lipoprotein-associated phospholipase A2 activities: relation to atherosclerotic plaques and future all-cause mortality. European Heart Journal. 2012;33(23):2946-2954.