Effect of clopidogrel pretreatment on inflammatory marker expression in patients undergoing percutaneous coronary intervention

被引:123
作者
Quinn, MJ
Bhatt, DL
Zidar, F
Vivekananthan, D
Chew, DP
Ellis, SG
Plow, E
Topol, EJ
机构
[1] Cleveland Clin Fdn, Dept Cardiovasc Med, Joseph J Jacobs Ctr Thrombosis & Vasc Biol, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Joseph J Jacobs Ctr Thrombosis & Vasc Biol, Dept Mol Cardiol, Cleveland, OH 44195 USA
[3] St Vincents Univ Hosp, Dublin, Ireland
[4] Flinders Med Ctr, Dept Cardiovasc Med, Bedford Pk, SA, Australia
关键词
D O I
10.1016/j.amjcard.2003.11.048
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Platelets play an important role in the inflammatory response. In a nonrandomized comparison, we examined the effect of clopidogrel pretreatment on platelet inflammatory marker expression in patients undergoing percutaneous coronary intervention (PCI). Platelet expression of the inflammatory markers CD40 ligand (L) and CD62 P-selectin (P) and serum levels of interleukin-6 and CD40L were compared in patients pretreated (>24 hours before PCI) or not pretreated with clopidogrel. Blood samples were obtained before and after the procedure, and from 18 to 24 hours later. Marker expression in resting and adenosine diphosphate (ADP) (50 mumol/L.) and thrombin receptor activating peptide (TRAP) (10 mumol/L) activated samples was quantified by flow cytometry. Serum CD40L and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay. Seventy-nine patients were recruited into the study. Forty-two percent were pretreated with clopidogrel for a median of 5 days (range 1 to 1,325). Clopidogrel pretreatment was associated with lower ADP-activated platelet CD40L expression in baseline and postprocedural samples. Similarly, platelet CD62P expression at all time points in ADP-activated and in baseline and postprocedural. TRAP-activated samples was lower in patients pretreated with clopidogrel. These differences remained after multivariate adjustment between the groups. Serum CD40L levels increased from 2.13 +/- 2.37 ng/ml at baseline to 4.77 +/- 3.86 ng/ml at 18 to 24 hours after the procedure (p <0.0001). Similarly, serum IL-6 levels increased at 18 to 24 hours after the procedure (14.8 +/- 42.0 pg/ml before vs 25.5 +/- 36.0 pg/ml at 18 to 24 hours after the procedure, p <0.0001). Clopidogrel pretreatment did not affect serum IL-6 or CD40L levels. Thus, clopidogrel pretreatment reduces platelet inflammatory marker expression in patients undergoing PCI. (C) 2004 by Excerpta Medica, Inc.
引用
收藏
页码:679 / 684
页数:6
相关论文
共 28 条
[1]   CD40L stabilizes arterial thrombi by a β3 integrin-dependent mechanism [J].
André, P ;
Prasad, KSS ;
Denis, CV ;
He, M ;
Papalia, JM ;
Hynes, RO ;
Phillips, DR ;
Wagner, DD .
NATURE MEDICINE, 2002, 8 (03) :247-252
[2]   Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban) [J].
Assali, AR ;
Salloum, J ;
Sdringola, S ;
Moustapha, A ;
Ghani, M ;
Hale, S ;
Schroth, G ;
Fujise, K ;
Anderson, HV ;
Smalling, RW ;
Rosales, OR .
AMERICAN JOURNAL OF CARDIOLOGY, 2001, 88 (08) :884-+
[3]   Platelet and leukocyte deactivation after intracoronary stent placement in patients receiving combined antiplatelet therapy [J].
Atalar, E ;
Aytemir, K ;
Haznedaroglu, I ;
Aksöyek, S ;
Övünç, K ;
Kirazli, S ;
Özmen, F .
CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS, 2001, 7 (02) :116-121
[4]   Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina -: Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes [J].
Aukrust, P ;
Müller, F ;
Ueland, T ;
Berget, T ;
Aaser, E ;
Brunsvig, A ;
Solum, NO ;
Forfang, K ;
Froland, SS ;
Gullestad, L .
CIRCULATION, 1999, 100 (06) :614-620
[5]   Scientific and therapeutic advances in antiplatelet therapy [J].
Bhatt, DL ;
Topol, EJ .
NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (01) :15-28
[6]   Need to test the arterial inflammation hypothesis [J].
Bhatt, DL ;
Topol, EJ .
CIRCULATION, 2002, 106 (01) :136-140
[7]   Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein [J].
Chew, DP ;
Bhatt, DL ;
Robbins, MA ;
Mukherjee, D ;
Roffi, M ;
Schneider, JP ;
Topol, EJ ;
Ellis, SG .
AMERICAN JOURNAL OF CARDIOLOGY, 2001, 88 (06) :672-674
[8]   Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention [J].
Chew, DP ;
Bhatt, DL ;
Robbins, MA ;
Penn, MS ;
Schneider, JP ;
Lauer, MS ;
Topol, EJ ;
Ellis, SG .
CIRCULATION, 2001, 104 (09) :992-997
[9]   Death following creatine kinase-MB elevation after coronary intervention - Identification of an early risk period: Importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy [J].
Ellis, SG ;
Chew, D ;
Chan, A ;
Whitlow, PL ;
Schneider, JP ;
Topol, EJ .
CIRCULATION, 2002, 106 (10) :1205-1210
[10]   Effects of abciximab, ticlopidine, and combined abciximab/ticlopidine therapy on platelet and leukocyte function in patients undergoing coronary angioplasty [J].
Fredrickson, BJ ;
Turner, NA ;
Kleiman, NS ;
Graziadei, N ;
Maresh, K ;
Mascelli, MA ;
Effron, MB ;
McIntire, LV .
CIRCULATION, 2000, 101 (10) :1122-1129