Abstract
Background: Elevated C‐reactive protein (CRP) has been found to correlate with higher risk for cardiac events in patients with acute myocardial infarction (AMI). It has been suggested that CRP may be involved in initiation process of coagulation; however, the role of CRP level in the formation of left ventricular (LV) thrombus has not been studied.
Hypothesis: This study investigated whether CRP is a risk factor for LV thrombus in patients with AMI.
Methods: Clinical, echocardiography, and biochemical data were analyzed in 141 consecutive patients (aged 57 ± 13 years; 33 women) with first anterior AMI. Two‐dimensional and Doppler echocardiographic examinations were performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained every day during hospitalization. Serum CRP concentrations were measured by an ultrasensitive immunonephelometry method.
Results: Left ventricular thrombus was detected in 33 (23.4%) patients. Univariate analysis showed that patients with LV thrombus had a higher peak creatine kinase (CK) level (2879 ± 742 vs. 1693 ± 1210 I/U, p = 0.001), higher peak CRP level (14.9 ± 7.1 vs. 9.2 ± 6.8 mg/dl, p = 0.001), higher wall motion score index (1.8 ± 0.2 vs. 1.5 ± 0.3, p = 0.002), higher apical wall motion score index (2.35 ± 0.72 vs. 2.07 ± 0.70, p = 0.001), larger end‐diastolic volume (145.2 ± 43.7 vs. 116.5 ± 44.2 ml, p = 0.002), larger end‐systolic volume (85.4 ± 37.2 vs. 62.9 ± 31.6 ml, p = 0.003), and lower ejection fraction (42.1 ± 12 vs. 47.3 ± 13, p = 0.04). in multivariate analyses, only peak CK level (p = 0.0001), LV apical wall motion score index (p = 0.001), and CRP levels (p = 0.001) were independent predictors of LV thrombus formation.
Conclusions: These results suggest that CRP is a risk factor for LV thrombus in patients with AMI.
Keywords: C‐reactive protein, acute myocardial infarction, left ventricular thrombus
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References
- 1. Dantzig JMV, Delemarre BJ, Bot H, Visser CA: Left ventricular thrombus in acute myocardial infarction. Eur Heart J 1996; 17: 1640–1645 [DOI] [PubMed] [Google Scholar]
- 2. Friedman MJ, Carlson K, Marcus FI, Woolfenden JM: Clinical correlations in patients with acute myocardial infarction and left ventricular thrombus detected by two‐dimensional echocardiography. Am J Med 1982; 72: 894–898 [DOI] [PubMed] [Google Scholar]
- 3. Spirito P, Belloti P, Chiarella F, Domenicucci S, Sementa A, Vecchio C: Prognostic significance and natural history of left ventricular thrombi in patients with acute anterior myocardial infarction: A two‐dimensional echocardiographic study. Circulation 1985: 72: 774–780 [DOI] [PubMed] [Google Scholar]
- 4. Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB: Production of C‐reactive protein and risk of coronary events in stable and unstable angina. Lancet 1997: 349: 462–466 [DOI] [PubMed] [Google Scholar]
- 5. Pannitteri G, Marino B, Campa PP, Martucci R, Testa U, Peschle C: Interleukins 6 and 8 as mediators of acute phase response in acute myocardial infarction. Am J Cardiol 1997: 80: 623–625 [DOI] [PubMed] [Google Scholar]
- 6. Anzai T, Yoshikawa T, Shiraki H, Asakura Y, Akaishi M, Mitamura H, Ogawa S: C‐reactive protein as a predictor of infarct expansion and cardiac rupture after a first Q wave acute myocardial infarction. Circulation 1997: 96: 778–784 [DOI] [PubMed] [Google Scholar]
- 7. Ueda S, Ikeda U, Yamamoto K, Takahashi M, Nishinaga M, Nago N, Shimada K: C‐reactive protein as a predictor of cardiac rupture after myocardial infarction. Am Heart J 1996; 131: 857–860 [DOI] [PubMed] [Google Scholar]
- 8. Pietilä KO, Harmoinen AP, Jokiniitty J, Pasternac AI: Serum C‐reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow‐up in patients under thrombolytic treatment. Eur Heart J 1996; 17: 1345–1349 [DOI] [PubMed] [Google Scholar]
- 9. Linnanmäki E, Leinonen M Mattila K, Nieminen MS, Valtonen V Saikku P: Chlamydia pneumoniae‐specific circulating immune complexes in patients with chronic coronary heart disease. Circulation 1993: 87: 1130–1134 [DOI] [PubMed] [Google Scholar]
- 10. Asinger RW, Mikell FL, Elsperger J Hodges M: Incidence of left ventricular thrombosis after acute transmural myocardial infarction: Serial evaluation by two‐dimensional echocardiography. N Engl J Med 1981: 305: 297–302 [DOI] [PubMed] [Google Scholar]
- 11. Schiller N, Shall PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H Reichek N Sahn D Schnittger I: Recommendation for quantitation of the left ventricle by two dimensional echocardiography. J Am Soc Echocardiogr 1989: 2: 358–368 [DOI] [PubMed] [Google Scholar]
- 12. Ross T: The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 1993; 362: 801–809 [DOI] [PubMed] [Google Scholar]
- 13. Libby P: Molecular basis of the acute coronary syndromes. Circulation 1995: 91: 2844–2850 [DOI] [PubMed] [Google Scholar]
- 14. Ridker PM: C‐reactive protein and risk of future myocardial infarction and thrombotic stroke. Eur Heart J 1998; 19: 1–3 [DOI] [PubMed] [Google Scholar]
- 15. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A: The prognostic value of C‐reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994: 331: 417–424 [DOI] [PubMed] [Google Scholar]
- 16. Haverkate F, Thompson S, Duckert F: Haemostasis factors in angina pectoris: Relation to gender, age and acute‐phase reaction. Thromb Haemost 1995; 73: 561–567 [PubMed] [Google Scholar]
- 17. Kuller LH, Tracy RP, Shaten J, Meilahn EN: Relation of C‐reactive protein and coronary heart disease in the MRFIT nested case‐control study. Am J Epidemiol 1996; 144: 537–547 [DOI] [PubMed] [Google Scholar]
- 18. Heinrich J, Schulte H, Schönfeld R, Köhler E, Assmann G: Association of variables of coagulation, fibrinolysis and acute‐phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain. Thromb Haemostas 1995: 73: 374–378 [PubMed] [Google Scholar]
- 19. Toss H, Lindahl B, Siegbahn A, Wallentin L: Prognostic influence of increased fibrinogen and C‐reactive protein levels in unstable coronary artery disease. Circulation 1997; 96: 4204–4210 [DOI] [PubMed] [Google Scholar]
- 20. Pepys M: C‐reactive protein fifty years on. Lancet 1981; i: 653–656 [DOI] [PubMed] [Google Scholar]
- 21. Lagrant WK, Niessen JWM, Wolbink GJ, Jaspars EH, Visser CA, Verheugt FWA, Meijer CJLM, Hack CE: C‐reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 1997; 95: 97–103 [DOI] [PubMed] [Google Scholar]
- 22. Agrawal A, Kilpatrick JM, Volanakis JE: Structure and function of human C‐reactive protein In Acute Phase Proteins. Molecular Biology, Biochemistry, and Clinical Applications (Eds. Maekiewicz A, Kushner I, Baumann H.), p. 19–92. Boca Raton, Fla: CRC Press, Inc., 1993. [Google Scholar]
- 23. de Beer FC, Hind CRK, Fox KM, Allan RM, Maseri A, Pepys MB: Measurement of serum C‐reactive protein concentration in myocardial ischaemia and infarction. Br Heart J 1982: 47: 239–243 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Pietilä KO, Harmoinen AP, Hermens WT, Simoons ML van de Werf F, Verstraete M: Serum C‐reactive protein and infarct size in myocardial infarct patients with a closed versus an open infarct‐related coronary artery after thrombolytic therapy. Eur Heart J 1993; 14: 915–919 [DOI] [PubMed] [Google Scholar]
- 25. Heuertz RM, Piquette CA, Webster RO: Rabbits with elevated serum C‐reactive protein exhibit diminished neutrophil infiltration and vascular permeability in C5a‐induced alveolitis. Am J Pathol 1993; 142: 319–328 [PMC free article] [PubMed] [Google Scholar]
- 26. Volanakis JE: Complement activation by C‐reactive protein complexes. Ann N Y Acad Sci 1982; 389: 235–249 [DOI] [PubMed] [Google Scholar]
- 27. Kilgore KS, Friedrichs GS, Homeister JW, Lucchesi BR: The complement system in myocardial ischemia/reperfusion injury. Cardiovasc Res 1994: 28: 437–444 [DOI] [PubMed] [Google Scholar]
- 28. Pinckard RN, Olson MS, Giclas PC, Terry R Boyer JT O'Rourke RA: Consumption of classical complement components by heart subcellular membranes in vitro and in patients after acute myocardial infarction. J Clin Invest 1975; 56: 740–750 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Mathey D, Schofer J, Schäfer HJ, Hamdoch T, Joachim HC, Ritgen A, Hugo F, Bhakdi S: Early accumulation of the terminal complement‐complex in the ischaemic myocardium after reperfusion. Eur Heart J 1994; 15: 418–423 [DOI] [PubMed] [Google Scholar]
- 30. Engler RL, Schmid‐Schonbein GW, Pavelec RS: Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 1983; 111: 98–111 [PMC free article] [PubMed] [Google Scholar]
- 31. Carson SD, Johnson DR: Consecutive enzyme cascades: Complement activation at the cell surface triggers increased tissue factor activity. Blood 1990; 762: 361–367 [PubMed] [Google Scholar]
- 32. Hamilton KK, Hattori R, Esmon CT, Sims PJ: Complement proteins C5b‐9 induce vesuculation of the endothelial plasma membrane and expose catalytic surface for the assembly of the prothrombinase enzyme complex. J Biol Chem 1990; 256: 3809–3814 [PubMed] [Google Scholar]
- 33. Lagrand WK, Viser CA, Hermens WT, Niessen HW, Verheugt FW, Wolbink GJ, Hack CE: C‐reactive protein as a cardiovascular risk factor. Circulation 1999; 100: 96–102 [DOI] [PubMed] [Google Scholar]
- 34. Tommasi S, Carluccio E, Bentivoglio M, Buccolieri M, Mariotti M, Politano M, Corea L: C‐reactive protein as a marker for cardiac ischemic events in the year after a first, uncomplicated myocardial infarction. Am J Cardiol 1999: 83: 1595–1599 [DOI] [PubMed] [Google Scholar]
- 35. Pietilä K, Harmoinen A, Teppo A‐M: Acute phase reaction, infarct size and in‐hospital morbidity in myocardial infarction patients treated with streptokinase or recombinant tissue type plasminogen activator. Ann Med 1991; 23: 529–535 [DOI] [PubMed] [Google Scholar]
- 36. Arvan S: Left ventricular mural thrombi secondary to acute myocardial infarction: Predisposing factors and embolic phenomenon. J Clin Ultrasound 1983; 11: 467–473 [DOI] [PubMed] [Google Scholar]
- 37. Domenicucci S, Chiarella F, Bellotti P, Lupi G, Scarsi G, Vecchio C: Early appearance of left ventricular thrombi after anterior myocardial infarction: A marker of higher in‐hospital mortality in patients not treated with antithrombotic drugs. Eur Heart J 1990; 11: 51–58 [DOI] [PubMed] [Google Scholar]