C-Reactive Protein is Not Associated with Cardiovascular Events Following Percutaneous Coronary Intervention with Drug-Elu...
Introduction <ul><li>Inflammatory mechanisms play a central role in the pathogenesis of atherosclerosis.  </li></ul><ul><l...
<ul><li>The goal of this study was to extend prior observations by examining if baseline hsCRP is correlated with cardiova...
Hypothesis <ul><li>Elevated hsCRP would not be associated with increased incidence of cardiac death, myocardial infarction...
Methods <ul><li>Retrospective analysis of 1515 consecutive patients who underwent unrestricted PCI with ≥1 DES between Apr...
Methods <ul><li>353 patients had a hsCRP <1. </li></ul><ul><li>439 between 1 and 3. </li></ul><ul><li>461 between 3 and 10...
Methods <ul><li>Incidence of the following was examined up to 3 years following PCI: </li></ul><ul><ul><li>Cardiac Mortali...
Patient characteristics stratified by hsCRP levels   0.109 21.0±7.0 21.1±6.8 20.2±6.2 20.3±6.7 Stent length (mm) 0.263 3.0...
Cardiac death
Myocardial infarction
Target Vessel Revascularization
Results <ul><li>There was a higher incidence of all-cause mortality in the hsCRP>10 group compared to the other groups tha...
All-cause mortality
Discussion <ul><li>Baseline hsCRP is not independently associated with increased risk of cardiovascular events following i...
Discussion <ul><li>The result of this analysis differs from some prior studies that demonstrated differences in cardiovasc...
Discussion <ul><li>CAPTURE trial </li></ul><ul><ul><li>reported a high incidence of death and MI </li></ul></ul><ul><ul><l...
Discussion <ul><li>Several studies that have reported no association with hsCRP levels and restenosis. </li></ul><ul><li>R...
Drug-Eluting Stents <ul><li>One of the main differences between this analysis and those preceding.  </li></ul><ul><li>In t...
Drug-Eluting Stents <ul><li>Several studies have compared DES to BMS in the setting of analyzing the prognostic value of h...
Discussion <ul><li>The inflammatory process leading to plaque growth and rupture differs from the healing inflammatory pro...
Statins <ul><li>Treatment with statins significantly lowers hsCRP concentrations independent of their effects on serum lip...
Statins <ul><li>It could be speculated that the high prevalence of statin use diminished the potential predictive value of...
Limitations <ul><li>Non-randomized retrospective analysis, and as such it is possible that both identified and unidentifie...
Acknowledgements <ul><li>Dr. Ron Waksman </li></ul><ul><li>Dr. Tina Pinto Slottow </li></ul>
References <ul><li>Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999;340:115-26. </li></ul><ul><li>Ridke...
References <ul><li>Chew DP, Bhatt DL, Robbins MA, et al. Incremental prognostic value of elevated baseline C-reactive prot...
References <ul><li>Zhou YF, Csako G, Grayston JT, et al.  Lack of association of restenosis following coronary angioplasty...
References <ul><li>Dibra A, Mehilli J, Braun S, et al. Inflammatory response after intervention assessed by serial C-react...
References <ul><li>De la Torre-Hernandez J M, Sainz-Laso F, Burgos V, et al. Comparison of C-reactive protein levels after...
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medicine.georgetown.edu/residency/schola rly/HannaNick2.ppt

  1. 1. C-Reactive Protein is Not Associated with Cardiovascular Events Following Percutaneous Coronary Intervention with Drug-Eluting Stents at 3-Year Follow-Up Tina L Pinto Slottow MD, Nicholas Hanna MD, Daniel Steinberg MD, Probal Roy MD, Zhenyi Xue BS, Kimberly Kaneshige BS, Rebecca Torguson MS, Joseph Lindsay MD, Augusto Pichard MD, Lowell Satler MD, William Suddath MD, Kenneth Kent MD PhD, and Ron Waksman, MD Division of Cardiology, Washington Hospital Center, Washington, DC, USA
  2. 2. Introduction <ul><li>Inflammatory mechanisms play a central role in the pathogenesis of atherosclerosis. </li></ul><ul><li>Elevated hsCRP is a marker of inflammation that has been shown to be associated with adverse cardiovascular events. </li></ul><ul><li>Evaluation of the relationship between hsCRP and clinical outcomes following PCI have demonstrated mixed results. </li></ul>
  3. 3. <ul><li>The goal of this study was to extend prior observations by examining if baseline hsCRP is correlated with cardiovascular events following PCI with DES. </li></ul>Goal of study
  4. 4. Hypothesis <ul><li>Elevated hsCRP would not be associated with increased incidence of cardiac death, myocardial infarction, or target vessel revascularization in the DES era. </li></ul>
  5. 5. Methods <ul><li>Retrospective analysis of 1515 consecutive patients who underwent unrestricted PCI with ≥1 DES between April 2003 and January 2006. </li></ul><ul><li>Stratified by baseline hsCRP levels that were measured prior to stent implantation. </li></ul>
  6. 6. Methods <ul><li>353 patients had a hsCRP <1. </li></ul><ul><li>439 between 1 and 3. </li></ul><ul><li>461 between 3 and 10. </li></ul><ul><li>262 greater than 10. </li></ul>
  7. 7. Methods <ul><li>Incidence of the following was examined up to 3 years following PCI: </li></ul><ul><ul><li>Cardiac Mortality </li></ul></ul><ul><ul><li>Myocardial Infarction (MI) </li></ul></ul><ul><ul><li>Target Vessel Revascularization (TVR) </li></ul></ul>
  8. 8. Patient characteristics stratified by hsCRP levels 0.109 21.0±7.0 21.1±6.8 20.2±6.2 20.3±6.7 Stent length (mm) 0.263 3.0±0.8 3.0±0.4 3.0±0.8 3.0±0.3 Stent diameter (mm) 0.477 2.1±3.5 1.8±0.9 1.9±2.0 1.8±1.3 Lesions treated (number) 0.315 2.1±0.8 1.9±0.8 1.9±0.9 1.9±0.9 Diseased vessels (number) p value n=230 n=400 n=406 n=305 Angiographic characteristics 0.734 231 (97.5) 396 (98.5) 414 (98.6) 318 (98.1) Statin use <0.001 60 (23.2) 48 (11.3) 21 (4.6) 16 (4.8) MI during admission <0.001 58 (22.2) 59 (13.6) 34 (7.4) 24 (6.8) History of CRI <0.001 56 (23.1) 58 (14) 49 (11.3) 37 (10.9) History of CHF <0.001 50 (19.1) 95 (21.6) 64 (13.9) 31 (8.8) Current smoker 0.125 221 (84.4) 393 (90.1) 409 (89.1) 312 (88.6) Hypercholesterolemia 0.01 103 (39.6) 151 (34.7) 134 (29.4) 100 (28.6) Diabetes mellitus 0.642 219 (83.6) 365 (83.1) 376 (81.9) 282 (80.1) Hypertension 0.068 67.4±11.8 65.1±11.2 65.9±11.0 65.8±11.1 Age (years) <0.001 146 (55.7) 274 (62.4) 337 (73.1) 279 (79) Male <0.001 51.9±83.3 5.5±2.0 1.9±0.6 0.6±0.3 Baseline hsCRP p value n=262 n=439 n=461 n=353 Patient Characteristics, n (%) ≥ 10 3 to <10 1 to <3 <1 hsCRP
  9. 9. Cardiac death
  10. 10. Myocardial infarction
  11. 11. Target Vessel Revascularization
  12. 12. Results <ul><li>There was a higher incidence of all-cause mortality in the hsCRP>10 group compared to the other groups that was noted at 6 month follow-up and persisted to 3 year follow-up. </li></ul><ul><li>This mortality difference remained even following adjustment for the differences in baseline characteristics. </li></ul>
  13. 13. All-cause mortality
  14. 14. Discussion <ul><li>Baseline hsCRP is not independently associated with increased risk of cardiovascular events following intervention at 3 year follow-up. </li></ul><ul><li>As found in other evaluations of patient groups with very elevated hsCRP, comorbidities were more common in the CRP>10 group. </li></ul>
  15. 15. Discussion <ul><li>The result of this analysis differs from some prior studies that demonstrated differences in cardiovascular outcomes on hsCRP levels. </li></ul><ul><li>Nonetheless, there are other evaluations that correspond with the findings in this study. </li></ul>
  16. 16. Discussion <ul><li>CAPTURE trial </li></ul><ul><ul><li>reported a high incidence of death and MI </li></ul></ul><ul><ul><li>broad assignment of patients to either hsCRP positive or hsCRP negative groups </li></ul></ul><ul><ul><li>neither this, nor other smaller studies, have associated hsCRP with the need for repeat revascularization, which was one of the primary endpoints in this study. </li></ul></ul>
  17. 17. Discussion <ul><li>Several studies that have reported no association with hsCRP levels and restenosis. </li></ul><ul><li>Rittersma et al and Gomma et al found no statistically significant association with pre-procedural hsCRP levels and angiographic restenosis at 6 months. </li></ul><ul><ul><li>patient population was predominately composed of those with stable angina. </li></ul></ul>
  18. 18. Drug-Eluting Stents <ul><li>One of the main differences between this analysis and those preceding. </li></ul><ul><li>In the largest studies, only 40% of the de Winter et al population required PCI, while Dibra et al had only 23% of their subjects receiving DES. </li></ul>
  19. 19. Drug-Eluting Stents <ul><li>Several studies have compared DES to BMS in the setting of analyzing the prognostic value of hsCRP. </li></ul><ul><ul><li>Gibson et al is the largest study (n=741) which included three arms comparing BMS to two different DES individually and as a group. Among the moderate to high risk patients, DES implantation was associated with reductions in hsCRP and troponin level. </li></ul></ul>
  20. 20. Discussion <ul><li>The inflammatory process leading to plaque growth and rupture differs from the healing inflammatory process after PCI. </li></ul><ul><li>This may trigger strong inflammatory response and confound the utility of hsCRP as a dependable marker of future events. </li></ul>
  21. 21. Statins <ul><li>Treatment with statins significantly lowers hsCRP concentrations independent of their effects on serum lipids. </li></ul><ul><li>Widespread use of statins is sited in multiple studies that compare DES and BMS as a possible contributor to improving outcomes. </li></ul>
  22. 22. Statins <ul><li>It could be speculated that the high prevalence of statin use diminished the potential predictive value of the hsCRP level. </li></ul><ul><li>These findings have important therapeutic implications towards understanding outcomes after PCI. </li></ul><ul><li>Further studies would be needed to deduce if baseline hsCRP has any utility in the DES era. </li></ul>
  23. 23. Limitations <ul><li>Non-randomized retrospective analysis, and as such it is possible that both identified and unidentified confounders may have influenced the outcomes. </li></ul><ul><li>Type of stents used. </li></ul><ul><li>Size of population. </li></ul>
  24. 24. Acknowledgements <ul><li>Dr. Ron Waksman </li></ul><ul><li>Dr. Tina Pinto Slottow </li></ul>
  25. 25. References <ul><li>Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999;340:115-26. </li></ul><ul><li>Ridker PM. C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol 2007;49:2129-38. </li></ul><ul><li>Sukhija R, Fahdi I, Garza L, et al. Inflammatory markers, angiographic severity of coronary artery disease, and patient outcome. Am J Cardiol 2007;99:879-84. </li></ul><ul><li>Gach O, Legrand V, Biessaux Y, Chapelle JP, Vanbelle S, Pierard LA. Long-term prognostic significance of high-sensitivity C-reactive protein before and after coronary angioplasty in patients with stable angina pectoris. Am J Cardiol 2007;99:31-5. </li></ul><ul><li>Horne BD, Muhlestein JB, Strobel GG, Carlquist JF, Bair TL, Anderson JL. Greater pathogen burden but not elevated C-reactive protein increases the risk of clinical restenosis after percutaneous coronary intervention. Am Heart J 2002;144:491-500. </li></ul><ul><li>Veselka J, Prochazkova S, Duchonova R, Homolova I, Tesar D. Relationship of C-reactive protein to adverse cardiovascular events in patients treated by percutaneous coronary intervention for stable angina pectoris. Int Heart J 2005;46:195-204. </li></ul>
  26. 26. References <ul><li>Chew DP, Bhatt DL, Robbins MA, et al. Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention. Circulation 2001;104:992-7. </li></ul><ul><li>de Winter RJ, Koch KT, van Straalen JP, et al. C-reactive protein and coronary events following percutaneous coronary angioplasty. Am J Med 2003;115:85-90. </li></ul><ul><li>Heeschen C, Hamm CW, Bruemmer J, Simoons ML. Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis. CAPTURE Investigators. Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial. J Am Coll Cardiol 2000;35:1535-42. </li></ul><ul><li>Zairis MN, Ambrose JA, Manousakis SJ, et al. The impact of plasma levels of C-reactive protein, lipoprotein (a) and homocysteine on the long-term prognosis after successful coronary stenting: The Global Evaluation of New Events and Restenosis After Stent Implantation Study. J Am Coll Cardiol 2002;40:1375-82. </li></ul><ul><li>Dibra A, Mehilli J, Braun S, et al. Association between C-reactive protein levels and subsequent cardiac events among patients with stable angina treated with coronary artery stenting. Am J Med 2003;114:715-22. </li></ul><ul><li>de Winter RJ, Heyde GS, Koch KT, et al. The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty. Eur Heart J 2002;23:960-6. </li></ul>
  27. 27. References <ul><li>Zhou YF, Csako G, Grayston JT, et al. Lack of association of restenosis following coronary angioplasty with elevated C-reactive protein levels or seropositivity to Chlamydia pneumoniae. Am J Cardiol 1999;84:595-8, A8. </li></ul><ul><li>Walter DH, Fichtlscherer S, Sellwig M, Auch-Schwelk W, Schachinger V, Zeiher AM. Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation. J Am Coll Cardiol 2001;37:839-46. </li></ul><ul><li>Rittersma SZH, de Winter RJ, Koch KT, Schotborgh CE, Bax M, Heyde GS, et al. Preprocedural C-reactive protein is not associated with angiographic restenosis or target lesion revascularization after coronary stent placement. Clin Chem 2004;50:1589-1596. </li></ul><ul><li>Gibson CM, Karmpaliotis D, Kosmidou I, Murphy SA, Kirtane AJ, Budiu D, Ray KK, Herrmann HC, Lakkis N, Kovach R, French W, Blankenship J, Lui HH, Palabrica T, Jennings LK, Cohen DJ, Morrow DA; TIMI Study Group. Comparison of effects of bare metal versus drug-eluting stent implantation on biomarker levels following percutaneous coronary intervention for non-ST-elevation acute coronary syndrome. Am J Cardiol. 2006 May 15;97(10):1473-7. </li></ul><ul><li>Kim JY, Ko YG, Shim CY, Park S, Hwang KC, Choi D, Jang Y, Chung N, Shim WH, Cho SY. Comparison of effects of drug-eluting stents versus bare metal stents on plasma C-reactive protein levels. Am J Cardiol. 2005 Nov 15;96(10):1384-8. </li></ul><ul><li>Skowasch D, Jabs A, Andrie R, et al. Progression of native coronary plaques and in-stent restenosis are associated and predicted by increased pre-procedural C reactive protein. Heart 2005;91:535–6. </li></ul>
  28. 28. References <ul><li>Dibra A, Mehilli J, Braun S, et al. Inflammatory response after intervention assessed by serial C-reactive protein measurements correlates with restenosis in patients treated with coronary stenting. Am Heart J 2005;150:344–50. </li></ul><ul><li>Gomma A H, Hirschfield G M, Gallimore J RJr, et al. Preprocedural inflammatory markers do not predict restenosis after successful coronary stenting. Am Heart J 2004;147:1071–7. </li></ul><ul><li>Segev A, Kassam S, Buller C E, et al. Pre-procedural plasma levels of C-reactive protein and interleukin-6 do not predict late coronary angiographic restenosis after elective stenting. Eur Heart J 2004;25:1029–35. </li></ul><ul><li>Dibra A, Ndrepepa G, Mehilli J, et al. Comparison of C-reactive protein levels before and after coronary stenting and restenosis among patients treated with sirolimus-eluting versus bare metal stents. Am J Cardiol 2005;95:1238–40. </li></ul>
  29. 29. References <ul><li>De la Torre-Hernandez J M, Sainz-Laso F, Burgos V, et al. Comparison of C-reactive protein levels after coronary stenting with bare metal versus sirolimus-eluting stents. Am J Cardiol 2005;95:748–51. </li></ul><ul><li>Gaspardone A, Versaci F, Tomai F, et al. C-reactive protein, clinical outcome, and restenosis rates after implantation of different drug-eluting stents. Am J Cardiol 2006;97:1311–16. </li></ul><ul><li>Ridker PM, Rifai N, Lowenthal SP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 2001;103:1191-3 </li></ul><ul><li>Buffon A, Liuzzo G, Biasucci LM, Pasqualetti P, Ramazzotti V, Rebuzzi AG, et al. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999;34:1512-1521 </li></ul>

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