Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease

Nuccia Morici, Laura Farioli, Laura Michelina Losappio, Giulia Colombo, Michele Nichelatti, Donatella Preziosi, Gianluigi Micarelli, Fabrizio Oliva, Cristina Giannattasio, Silvio Klugmann, Elide Anna Pastorello, Nuccia Morici, Laura Farioli, Laura Michelina Losappio, Giulia Colombo, Michele Nichelatti, Donatella Preziosi, Gianluigi Micarelli, Fabrizio Oliva, Cristina Giannattasio, Silvio Klugmann, Elide Anna Pastorello

Abstract

Objective: To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).

Methods: We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2 years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.

Results: Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7 ng/mL (sensitivity 46%, specificity 84%).

Conclusions: In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.

Keywords: CORONARY ARTERY DISEASE.

Figures

Figure 1
Figure 1
Box plots show Sheffé-adjusted pairwise comparisons between patients with MACCE, patients without MACCE and healthy controls. MACCE, major adverse cardiovascular and cerebrovascular events.
Figure 2
Figure 2
ROC analysis for tryptase, hs-troponin, SYNTAX score and CRP. CRP, C reactive protein; hs, high-sensitive; ROC, receiver operating characteristic; SYNTAX, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery.

References

    1. van der Wal AC, Becker AE, van der Loos CM et al. . Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994;89:36–44. 10.1161/01.CIR.89.1.36
    1. Mulvihill NT, Foley JB. Inflammation in acute coronary syndromes. Heart 2002;87:201–4. 10.1136/heart.87.3.201
    1. Mulvihill NT, Boccalatte M, Foley JB. Inflammatory markers as predictors of clinical outcome in acute coronary syndromes. Minerva Cardioangiol 2002;50:656–9.
    1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135–43. 10.1161/hc0902.104353
    1. Mulvihill NT, Foley JB, Murphy RT et al. . Risk stratification in unstable angina and non-Q wave myocardial infarction using soluble cell adhesion molecules. Heart 2001;85:623–7. 10.1136/heart.85.6.623
    1. Liuzzo G, Biasucci LM, Gallimore JR et al. . The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994;331:417–24. 10.1056/NEJM199408183310701
    1. Blankenberg S, Rupprecht HJ, Bickel C et al. . Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation 2001;104:1336–42. 10.1161/hc3701.095949
    1. Duplàa C, Couffinhal T, Labat L et al. . Monocyte/macrophage recruitment and expression of endothelial adhesion proteins in human atherosclerotic lesions. Atherosclerosis 1996;121:253–66. 10.1016/0021-9150(95)05729-3
    1. Richardson PD, Davies MJ, Borm GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaque. Lancet 1989;2:941–4. 10.1016/S0140-6736(89)90953-7
    1. Cheng GC, Loree HM, Kamm RD et al. . Distribution of circumferential stress in ruptured and stable atherosclerotic lesions: a structural analysis with histopathological correlation. Circulation 1993;87:1179–87. 10.1161/01.CIR.87.4.1179
    1. Galli SJ. Biology of disease: new insights into “the riddle of the mast cells”: microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Invest 1990;62:5–3.
    1. Kokkonen JO, Kovanen PT. Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein. Proc Natl Acad Sci USA 1987;84:2287–91. 10.1073/pnas.84.8.2287
    1. Kovanen PT. Mast cell granule-mediated uptake of low density lipoproteins by macrophages: a novel carrier mechanism leading to the formation of foam cells. Ann Med 1991;23:551–9. 10.3109/07853899109150517
    1. Heikkilä HM, Lätti S, Leskinen MJ et al. . Activated mast cells induce endothelial cell apoptosis by a combined action of chymase and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 2008;28:309–14.
    1. Kaartinen M, Penttilä A, Kovanen PT. Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 1994;90: 1669–78. 10.1161/01.CIR.90.4.1669
    1. Laine P, Kaartinen M, Penttilä A et al. . Association between myocardial infarction and the mast cells in the adventitia of the infarct-related coronary artery. Circulation 1999;99:361–9. 10.1161/01.CIR.99.3.361
    1. Kervinen H, Kaartinen M, Mäkynen H et al. . Serum tryptase levels in acute coronary syndromes. Int J Cardiol 2005;104: 138–43. 10.1016/j.ijcard.2004.10.023
    1. van Haelst PL, Timmer JR, Crijns HJ et al. . No long-lasting or intermittent mast cell activation in acute coronary syndromes. Int J Cardiol 2001;78:75–80. 10.1016/S0167-5273(00)00475-7
    1. Deliargyris EN, Upadhya B, Sane DC et al. . Mast cell tryptase: a new biomarker in patients with stable coronary artery disease. Atherosclerosis 2005;178:381–6. 10.1016/j.atherosclerosis.2004.09.008
    1. Filipiak KJ, Tarchalska-Krynska B, Opolski G et al. . Tryptase levels in patients after acute coronary syndromes: the potential new marker of an unstable plaque? Clin Cardiol 2003;26:366–72.
    1. Xiang M, Sun J, Lin Y et al. . Usefulness of serum tryptase level as an independent biomarker for coronary plaque instability in a Chinese population. Atherosclerosis 2011;215:494–9. 10.1016/j.atherosclerosis.2011.01.006
    1. Pastorello EA, Morici N, Farioli L et al. . Serum tryptase: a new biomarker in patients with acute coronary syndrome? Int Arch Allergy Immunol 2014;164:97–105. 10.1159/000360164
    1. Pastorello EA, Farioli L, Losappio LM et al. . Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2 years. Clin Mol Allergy 2015;13:14–19. 10.1186/s12948-015-0013-0
    1. Thygesen K, Alpert JS, Jaffe AS et al. . Third universal definition of myocardial infarction. Eur Heart J 2012;33:2551–67. 10.1093/eurheartj/ehs184
    1. Sianos G, Morel MA, Kappetein AP et al. . The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005;1:219–27.
    1. Serruys PW, Onuma Y, Garg S et al. . Assessment of the SYNTAX score in the SYNTAX study. EuroIntervention 2009;5:50–6. 10.4244/EIJV5I1A9
    1. SYNTAX Score Working Group. SYNTAX Score Calculator [online algorithm]. (accessed 1 June 2009).
    1. Garg S, Sarno G, Serruys PW et al. , TRATEGY and MULTISTRATEGY Investigators. Prediction of 1-year clinical outcomes using the SYNTAX score in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a substudy of the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials. JACC Cardiovasc Interv 2011;4:66–75. 10.1016/j.jcin.2010.09.017
    1. Westwood M, van Asselt T, Ramaekers B et al. . High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain: a systematic review and cost-effectiveness analysis. Health Technol Assess 2015;19:1–234. 10.3310/hta19440
    1. Haaf P, Reichlin T, Twerenbold R et al. . Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays. Eur Heart J 2014;35:365–75. 10.1093/eurheartj/eht218
    1. Bot I, Biessen EA. Mast cells in atherosclerosis. Thromb Haemost 2011;820–4. 10.1160/TH11-05-0291
    1. Meng Z, Yan C, Deng Q et al. . Oxidized low-density lipoprotein induces inflammatory responses in cultured human mast cells via toll-like receptor 4. Cell Physiol Biochem 2013;31:842–53. 10.1159/000350102
    1. Lee-Rueckert M, Kovanen PT. The mast cell as a pluripotent HDL-modifying effector in atherogenesis: from in vitro to in vivo significance. Curr Opin Lipidol 2015;26:362–8. 10.1097/MOL.0000000000000224
    1. Chen C, Khismatullin DB. Oxidized low density lipoprotein contributes to atherogenesis via co-activation of macrophages and mast cells. PLoS ONE 2015;10:e0123088 10.1371/journal.pone.0123088
    1. Vafaie M, Slagman A, Möckel M et al. . Prognostic value of undetectable hs troponin T in suspected acute coronary syndrome. Am J Med 2016;129:274–82. 10.1016/j.amjmed.2015.10.016
    1. Deb S, Wijeysundera HC, Ko DT et al. . Coronary artery bypass graft surgery vs percutaneous interventions in coronary revascularization: a systematic review. JAMA 2013;310:2086–95. 10.1001/jama.2013.281718

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere