Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction

Luis Sargento; Carlota Saldanha; José Monteiro; Carlota Perdigão; J. Martins e Silva

doi:10.1160/TH04-12-0791

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(02): 380-388
DOI: 10.1160/TH04-12-0791

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction

Authors

Luis Sargento

¹Instituto de Bioquímica, Unidade de Biopatologia Vascular-IMM, Faculdade de Medicina de Lisboa. UTIC-AC, Serviço de Cardiologia, Hospital de Santa Maria, Lisboa, Portugal
Carlota Saldanha

¹Instituto de Bioquímica, Unidade de Biopatologia Vascular-IMM, Faculdade de Medicina de Lisboa. UTIC-AC, Serviço de Cardiologia, Hospital de Santa Maria, Lisboa, Portugal
José Monteiro

¹Instituto de Bioquímica, Unidade de Biopatologia Vascular-IMM, Faculdade de Medicina de Lisboa. UTIC-AC, Serviço de Cardiologia, Hospital de Santa Maria, Lisboa, Portugal
Carlota Perdigão

¹Instituto de Bioquímica, Unidade de Biopatologia Vascular-IMM, Faculdade de Medicina de Lisboa. UTIC-AC, Serviço de Cardiologia, Hospital de Santa Maria, Lisboa, Portugal
J. Martins e Silva

¹Instituto de Bioquímica, Unidade de Biopatologia Vascular-IMM, Faculdade de Medicina de Lisboa. UTIC-AC, Serviço de Cardiologia, Hospital de Santa Maria, Lisboa, Portugal

Abstract

Summary

The objective of this study was to evaluate the long-term predictive value of the haemostatic,inflammatory and haemorheologic disturbances in transmural myocardial infarction (MI). Sixty-four (59 male) consecutive survivors of a MI, with a mean age of 58.3 ± 12.0 years, were followed over a period of 36 months. Eighteen patients had a cardiovascular event defined as the composite of death, non-fatal MI, unstable angina and stroke. The haemostatic (protein C activity-PtC, antithrombin III, plasminogen activator inhibitor-1), haemorheologic (blood fluidity and components, erythrocyte membrane fluidity) and inflammatory (polymorphonuclear elastase, leukocyte count) profiles were determined at hospital discharge, using standard methodology. Our results can be summarized as follow: (i) at hospital discharge, the subgroup of patients with events had higher leuko-cyte count (7833.0 ± 1696.0 vs. 10294.0 ± 3129.0; p= 0.011), lower PtC (100.65 ± 19.08 vs.81.25 ± 19.95;p = 0.002),and lower erythrocyte aggregation (14.26 ± 5.94 vs.11.47 ± 3.45;p = 0.031) in relation to the ones without events;(ii) By Cox regression the protein C activity lower tertile (OR 0.169; 0.045 – 0.628; p=0.008); erythrocyte membrane outer layer fluidity upper tertile (OR 0.067; 95% CI 0.011 – 0.393; p=0.003); and erythrocyte aggregation lower tertile (OR 0.182; 0.038 – 0.876; p= 0.034) were independent predictors of the composite endpoint. We can conclude that some haemostatic, haemorheologic and inflammatory disturbances,at hospital discharge,are long-term independent predictors of recurrent cardiovascular events in transmural myocardial infarction survivors.

Keywords

Acute myocardial infarction - erythrocyte aggregation - protein C activity - leukocyte count - membrane fluidity - prognosis

Full Text

References

References
1 Baker I, Pickering J, Elwood P. et al. Fibrinogen, viscosity and white blood cell count predict myocardial, but not cerebral infarction: Evidence from the Caerphilly and Speedwell cohort. Thromb Haemost 2002; 87: 421-5.
2 Lowe G, Rumley A, Norrie J. et al. WOSKOPS. Blood rheology, cardiovascular risk factors and cardiovascular disease: The West of Scotland Coronary Prevention Study. Thromb Haemost 2000; 84: 553-8.
3 Sargento L, Saldanha C, Monteiro J. et al. Biohemorheologic factors and the cardiovascular events curve in transmural myocardial infarction survivors. 24 months follow-up. Rev Port Cardiol 2002; 21: 165-71.
4 Kesmarky G, Toth K, Habon L. et al. Hemorheological parameters in coronary arety disease. Clin Hemorheol Microc 1998; 18: 245-51.
5 Thompson SG, Kienast J, Stephen DM. et al. Haemostatic factors and the risk of myocardial infarction and sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-41.
6 Wiman B, Anderson T, Hallqvist J. et al. Plasma levels of tissue plasminogen activator / plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk factors for recurrent myocardial infarction in the Stockholm Heart Epidemology Program (SHEEP) study. Arterioscler Thromb Vasc Biol 2000; 20: 2019-23.
7 Yamada S, Yamada R, Ishii A. et al. Evaluation of tissue plasminogen activator and plasminogen activator inhibitor-I levels in acute myocardial infarction. J. Cardiol 1996; 27: 171-8.
8 Cushman M, Lemaitre RN, Kuller LH. et al. Fibrinolytic activation markers predict myocardial infarc- tion in the elderly. The Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999; 19: 493-8.
9 Juhan-Vague I, Pyke SD, Alessi MC. et al. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectors. ECAT Study group. European concerted action on Thrombosis and Disabilities. Circulation 1996; 94: 2057-63.
10 Smith FB, Fowkes FG, Rumley A. et al. Tissue plasminogen activator and leukocyte elastase as predictors of cardiovascular events in subjects with angina pectoris: Edinburgh Artery Study. Eur Heart J 2000; 21: 1607-13.
11 Baskurt OK, Levi E, Çaglayan S. et al. The role of hemorheologic factors in the coronary circulation. Clin Hemorheol 1991; 11: 121-7.
12 Saldanha C, Sargento L, Monteiro J. et al. Impairment of the erythrocyte membrane fluidity in survivors of acute myocardial infarction. A prospective study. Clin Hemorheol Microc 1999; 20: 111-6.
13 Koenig JW, Sund M, Lowe GDO. et al. Geographical variations in plasma viscosity and relation to coronary event rates. Lancet 1994; 334: 711-4.
14 Sargento L, Saldanha C, Monteiro J. et al. Evidence of prolonged disturbances in the haemostatic, haemorheologic and inflammatory profiles in transmural myocardial infarction survivors. A 12 months follow-up study. Thromb Haemost 2003; 89: 892-903.
15 Demple CE, Kortny F, Abildgaard V. Predictive value of coagulation markers concerning clinical outcome 90 days after anterior myocardial infarction. Thromb Haemost 1999; 81: 701-4.
16 Erikssen G, Liestol K, Bjonholt JV. et al. Erythrocyte sedimentation rate: a possible marker of atherosclerosis and a strong predictor of coronary heart disease mortality. Eur Heart J 2000; 21: 1614-20.
17 Lowe GDO, Drummond MM, Lorimer AR. et al. Relations between extent of coronary artery disease and blood viscosity. Br Med J 1980; 1: 673-4.
18 Sedzwyl S, Thomas M, Schilinfford J. Some observations on haematocrit changes in patients with myocardial infarction. Br Heart J 1968; 30: 344-9.
19 Dietzel J, Bang HO, Thorsen N. Myocardial infarction and whole blood viscosity. Acta Med Scand 1968; 183: 577-9.
20 Cesari M, Rossi GP. Plasminogen activator inhibitor 1 in ischemic cardiomiopathy. Arterioscler Thromb Vasc Biol 1999; 19: 1378-86.
21 Danesh J, Collins R, Peto R. et al. Haematocrit, viscosity, erythrocyte sedimentation rate: meta-analysis of prospective studies of coronary heart disease. Eur Heart J 2000; 21: 515-20.
22 Grzywacz A, Elikowski W, Psuja P. et al. Impairment of plasma fibrinolysis in young survivors of myocardial infarction with silent ischemia. Blood Coagul Fibrinolysis 1998; 9: 245-9.
23 Ioannido u-Papayannaki E, Lefkos N, Boudonas G. et al. Alterations in the fibrinolytic system components during acute myocardial infarction. Acta Cardiol 2000; 55: 247-53.
24 Koenig W, Sund M, Filipiak B. et al. Plasma viscosity and the risk of coronary heart disease. Results from the MONICA-Augsburg cohort study. Arterioscler Thromb Vasc Biol 1998; 18: 768-72.
25 Lowe GDO. Haemostatic risk factors for arterial and venous thrombosis. Pollere L, Ludlan CA. Recent advances in blood coagulation.. 7th Edinburgh: Churchill Livingstone; 1997: 69-96.
26 Petaya JM, Griffin JH. Activated protein C resistance: what have we learned now that the dust have settled?. Ann Intern Med 1997; 29: 469-72.
27 Ridker P. Fibrinolytic and inflammatory markers for arterial occlusion: The evolving epidemology of thrombosis and hemostasis. Thromb Haemost 1997; 78: 53-9.
28 Sinkovic A. Prognostic role of plasminogen activator inhibitor 1 levels in treatment with streptokinase of patients with acute myocardial infarction. Clin Cardiol 2000; 23: 486-9.
29 Goldstein JA, Demetriou D, Grines OL. et al. Multiple complex coronary plaques in patients with AMI. N Engl J M 2000; 343: 915-22.
30 Taylor FB, Chan A, Esmon CT. et al. Protein C prevents the coagulopathic and lethal effects of E. Coli infusion in the baboon. J Clin Invest 1987; 79: 918-25.
31 Van der Born JG, Bots ML, Haverkate F. Reduced response to activated protein C associated with increased risk of cerebrovascular disease. Ann Intern Med 1996; 25: 265-9.
32 Lowe GDO. Blood rheology and arterial disease. Clin Sci 1986; 71: 137-46.
33 Esmon CT, Owen WG. Identification of an endothelium cell cofactor for thrombin catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2246-52.
34 Wolin MS, Rodenberg JM, Messina EJ. et al. Oxygen metabolites and vasomotor mechanisms in rat cremasteric arterioles. Am J Physiol 1987; 252: H1159-H1163.
35 Walker FJ. Regulation of activated protein C by a new protein: a role for bovine protein S. J Biol Chem 1980; 255: 5521-4.
36 Regan LM, Lamphear BJ, Huggins CF. et al. Protein Ixa protects factor VIIIa from activated protein C. J Biol Chem 1994; 269: 9445-52.
37 Espana F, Vaya A, Mira Y. et al. Low level of circulating activated protein C is a risk factor for venous tromboembolism. Thromb Haemost 2001; 86: 1368-71.
38 Watanabe R, Wada H, Sakakura M. et al. Plasma levels of activated protein C inhibitor complex in patients with hypercoagulable states. Am J Hematol 2000; 65: 35-40.
39 Rosendaal FR, Sisconick DS, Schwartz SM. et al. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 89: 2817-21.
40 Ganapathyraman L, Shanthi P, Baba Krishnan K. et al. Protein C levels in ischemic heart disease. Indian Heart J 1996; 48: 125-7.
41 Rivard GE, David M, Farrell C. et al. Treatment of purpura fulminants in meningococcemia with protein C concentrates. J Pediatr 1995; 126: 646-52.
42 Powards D, Larsen R, Johnson J. et al. Epidemic meningococcemia and purpura fulminants with induced protein C deficiency. Clin Infect Dis 1993; 17: 254-61.
43 Esmon CT. Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflamation. Crit Care Med 2001; 29: S48-S51.
44 Gallaghen KP, Osaka G, Matsuzaki M. et al. Myocardial blood flow and function with critical coronary stenosis in exercising dogs. Am J Physiol 1982; 243: H698-H707.
45 Arntz HR, Roll G, Heitz J. et al. Effects of different thrombolytic agents on blood rheology in acute myocardial infarction. Clin Hemorheol 1991; 11: 63-78.
46 Sobral do Rosario H, Saldanha C, Martins e, Silva J. Increased leukocyte-endothelial interaction in the mesenteric microcirculation following remote ischemia-reperfusion. Microvasc Res 1999; 57: 199-202.
47 Vaya A, Falcó C, Fernadez P. et al. Erythrocyte aggregation determined with the Myrenne Aggregometer at two modes (M0, M1) and two times (5 and 10 sec). Clin Hemorheol Microcirc 2003; 29: 119-27.
48 Vaya A, Falcó C, Reganon E. et al. Influence of plasma proteins and erythrocyte factors on red blood cell aggregation in survivors of acute myocardial infarction. Thromb Haemost 2004; 91: 354-9.
49 Sargento L, Monteiro J, Saldanha C. et al. Erythrocyte deformability by ektacitometry in myocardial infarction survivors. Rev Port Cardiol 1996; 15: 935-6.
50 Peyrou V, Lormeau JC, Hérault JP. et al. Contribution of erythrocytes to thrombin generation in whole blood. Thromb Haemost 1999; 81: 400-6.
51 Wood BL, Gibson DF, Tait JF. Increased erythrocyte phosphatidylserine exposure in sickle cell disease: flow-cytometric measurement and clinical associations. Blood 1996; 88: 1873-6.
52 Sargento L, Saldanha C, Martins e, Silva J. Centrifugous force influence on erythrocyte aggregation. In vitro study in blood from stroke and diabetes mellitus patients (Abstract). Clin Hemorheol and Microcirc 1995; 32: 518. 9th European Conference Clinical Hemorheology.