History of previous bleeding and C-reactive protein improve assessment of bleeding risk in elderly patients (≥80 years) with myocardial infarction

Summary

We aimed to assess whether the CRUSADE risk score represents a robust instrument for stratification of bleeding risk in elderly myocardial infarction (MI) patients (≥80 years) and further aimed to identify age-specific predictors of major bleeding events. Binary logistic regression models were applied to assess the effect of variables on the occurrence of bleeding events during hospital stay. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory power. Out of 387 patients in the final study cohort, 74 patients (19.1 %) experienced a major bleeding event according to the definition of the International Society on Thrombosis and Haemostasis. The CRUSADE risk score demonstrated only a weak discriminatory power to predict bleeding in this group of patients (area under the ROC curve: 0.57 [0.51–0.65]; p=0.05). In the multivariate regression analysis, history of bleeding with an adjusted hazard ratio (HR) of 3.21(95 % confidence interval: 1.29–8.03, p=0.01) and C-reactive protein with an adjusted HR per increase of 10 mg/l of 1.05 (1.01–1.10) were independent predictors of major bleeding. Integration of both variables into the CRUSADE score demonstrated a significantly improved performance for bleeding as indicated by a significant increase in the ROC analysis (area under the curve: 0.64 vs 0.57; for comparison p<0.045), net reclassification index (35.6 0 %; p=0.006) and integrated discrimination increment (0.0242; p=0.02). In conclusion, bleeding history and C-reactive protein significantly improve the modest predictive power of the CRUSADE risk score in elderly patients with MI. These results point towards a specific risk profile for bleeding events in this high-risk group of patients.

Keywords

Aging - risk factors - ischaemic heart disease - inflammatory mediators

• References

• 1 Ruff CT, Braunwald E. The evolving epidemiology of acute coronary syndromes. Nat Rev Cardiol 2011; 8: 140-147.
• 2 Lee PY, Alexander KP, Hammill BG. et al. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. J Am Med Assoc 2001; 286: 708-713.
• 3 Alexander KP, Newby LK, Armstrong PW. et al. Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation 2007; 115: 2570-2589.
• 4 Alexander KP, Newby LK, Cannon CP. et al. Acute coronary care in the elderly, part I: Non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation 2007; 115: 2549-2569.
• 5 Yan RT, Yan AT, Tan M. et al. Age-related differences in the management and outcome of patients with acute coronary syndromes. Am Heart J 2006; 151: 352-359.
• 6 Moscucci M, Fox KA, Cannon CP. et al. Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2003; 24: 1815-1823.
• 7 Ndrepepa G, Berger PB, Mehilli J. et al. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 2008; 51: 690-697.
• 8 Chhatriwalla AK, Amin AP, Kennedy KF. et al. Association between bleeding events and in-hospital mortality after percutaneous coronary intervention. J Am Med Assoc 2013; 309: 1022-1029.
• 9 Rao SV, Dai D, Subherwal S. et al. Association between periprocedural bleeding and long-term outcomes following percutaneous coronary intervention in older patients. JACC Cardiovasc Interv 2012; 5: 958-965.
• 10 Marso SP, Amin AP, House JA. et al. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. J Am Med Assoc 2010; 303: 2156-2164.
• 11 Ariza-Sole A, Salazar-Mendiguchia J, Lorente V. et al. Predictive ability of bleeding risk scores in the routine clinical practice. Eur Heart J Acute Cardiovasc Care. 2014 Epub ahead of print.
• 12 Abu-Assi E, Raposeiras-Roubin S, Lear P. et al. Comparing the predictive validity of three contemporary bleeding risk scores in acute coronary syndrome. Eur Heart J Acute Cardiovasc Care 2012; 1: 222-231.
• 13 Ariza-Sole A, Formiga F, Lorente V. et al. Efficacy of bleeding risk scores in elderly patients with acute coronary syndromes. Rev Esp Cardiol 2014; 67: 463-470.
• 14 Faustino A, Mota P, Silva J.. Non-ST-elevation acute coronary syndromes in octogenarians: Applicability of the GRACE and CRUSADE scores. Rev Port Cardiol. 2014 Epub ahead of print.
• 15 Thygesen K, Alpert JS, Jaffe AS. et al. Third universal definition of myocardial infarction. Eur Heart J 2012; 33: 2551-2567.
• 16 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
• 17 Mehran R, Rao SV, Bhatt DL. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123: 2736-2747.
• 18 Yusuf S, Zhao F, Mehta SR. et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494-502.
• 19 Lagor C, Elliott CG, Stoddard GJ. et al. Weaknesses in the classification criteria for antithrombotic-related major bleeding events. Thromb Haemost 2005; 94: 997-1003.
• 20 Lopes RD, Subherwal S, Holmes DN. et al. The association of in-hospital major bleeding with short-, intermediate-, and long-term mortality among older patients with non-ST-segment elevation myocardial infarction. Eur Heart J 2012; 33: 2044-2053.
• 21 Subherwal S, Bach RG, Chen AY. et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation 2009; 119: 1873-1882.
• 22 Ducrocq G, Schulte PJ, Becker RC. et al. Association of spontaneous and procedure-related bleeds with short- and long-term mortality after acute coronary syndromes: an analysis from the PLATO trial. EuroIntervention. 2014 Epub ahead of print.
• 23 Kirkwood TB. Understanding the odd science of aging. Cell 2005; 120: 437-447.
• 24 Segev A, Strauss BH, Tan M. et al. Predictors and 1-year outcome of major bleeding in patients with non-ST-elevation acute coronary syndromes: insights from the Canadian Acute Coronary Syndrome Registries. Am Heart J 2005; 150: 690-694.
• 25 Poli D, Antonucci E, Testa S. et al. Bleeding risk in very old patients on vitamin K antagonist treatment: results of a prospective collaborative study on elderly patients followed by Italian Centres for Anticoagulation. Circulation 2011; 124: 824-829.
• 26 Poli D, Antonucci E, Testa S. et al. The predictive ability of bleeding risk stratification models in very old patients on vitamin K antagonist treatment for venous thromboembolism: results of the prospective collaborative EPICA study. J Thromb Haemost 2013; 11: 1053-1058.
• 27 Poli D, Antonucci E, Zanazzi M. et al. Impact of glomerular filtration estimate on bleeding risk in very old patients treated with vitamin K antagonists. Results of EPICA study on the behalf of FCSA (Italian Federation of Anticoagulation Clinics). Thromb Haemost 2012; 107: 1100-1106.
• 28 Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 2006; 47 (8 Suppl) C19-31.
• 29 Tuomisto K, Jousilahti P, Sundvall J. et al. C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study. Thromb Haemost 2006; 95: 511-518.
• 30 James SK, Armstrong P, Barnathan E. et al. Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome: a GUSTO-IV substudy. J Am Coll Cardiol 2003; 41: 916-924.
• 31 Blake GJ, Ridker PM. C-reactive protein and other inflammatory risk markers in acute coronary syndromes. J Am Coll Cardiol 2003; 41 (4 Suppl S) 37S-42S.
• 32 Liuzzo G, Buffon A, Biasucci LM. et al. Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina. Circulation 1998; 98: 2370-2376.
• 33 Freitas WM, Carvalho LS, Moura FA. et al. Atherosclerotic disease in octogenarians: a challenge for science and clinical practice. Atherosclerosis 2012; 225: 281-289.
• 34 Ndrepepa G, Neumann FJ, Schulz S. et al. Incidence and prognostic value of bleeding after percutaneous coronary intervention in patients older than 75 years of age. Catheter Cardiovasc Interv 2014; 83: 182-189.
• 35 Cambien B, Bergmeier W, Saffaripour S. et al. Antithrombotic activity of TNF-alpha. J Clin Invest 2003; 112: 1589-1596.
• 36 Campbell CL, Steinhubl SR, Hooper WC. et al. Bleeding events are associated with an increase in markers of inflammation in acute coronary syndromes: an ACUITY trial substudy. J Thromb Thrombolysis 2011; 31: 139-145.
• 37 De Luca G, Navarese E, Marino P. Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials. Eur Heart J 2009; 30: 2705-2713.