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Coronary stent implantation may seal the inflammatory response in patients with acute coronary syndromes
International Journal of Cardiology 130 (2008) 503 – 504 www.elsevier.com/locate/ijcard
Letter to the Editor
Coronary stent implantation may seal the inflammatory response in patients with acute coronary syndromes Marco V. Wainstein a,⁎, Diego P. Bento da Silva a , Jorge P. Ribeiro a,b a
b
Cardiology Division, Hospital de Clínicas de Porto Alegre, Brazil Department of Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil Received 1 June 2007; accepted 1 July 2007 Available online 4 October 2007
Abstract The change in CD40L levels before and 24 h coronary stenting was compared in patients presenting with acute coronary syndromes and for elective angioplasty. Baseline CD40L levels were lower in stable subjects, whereas unstable patients had a significant decrease of CD40L after stenting. This might suggest that coronary stenting, despite of being a local therapy, can help to seal a systemic inflammatory response in acute coronary syndromes. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: CD40; Stent; Acute coronary syndromes
Plaque vulnerability may involve a systemic inflammatory state which includes multiple interactions between leucocytes, endothelial cells, and platelets [1–4]. Recent data suggests that CD40L may be the cornerstone of this process [4]. CD40L is a trimetric transmembrane protein from the tumor necrosis factor family, which was originally identified in the immune system, but is also present in the endothelial and inflammatory cells, as well as in activated platelets [5,6]. The association of CD40L and platelets is capable of inducing an inflammatory response and ultimately to promote matrix degradation and plaque rupture [7]. Elevated levels of CD40L can help to identify patients with ACS that are at higher risk of cardiovascular adverse events, regardless of other markers of myocardial ischemia, such as creatine kinase-Mb and troponins [8]. Despite the fact that coronary stent implantation offers a local therapeutic alternative, it is controversial if this could lead to a systemic reduction of plaque vulnerability,[9] rather to increase the inflammatory response locally [10]. ⁎ Corresponding author. Cardiology Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350 90035-003, Porto Alegre, RS Brazil. Tel.: +55 51 9916 0826; fax: +55 51 2101 8621. E-mail address: [email protected] (M.V. Wainstein). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.07.051
We conducted a prospective, observational study. Patients of both genders, aged 18 to 75 years, referred for stent implantation were recruited. According to clinical presentation, patients were divided in two groups: stable angina and/or silent myocardial ischemia as detected on functional tests (stable); and high-risk non-ST-elevation ACS (ACS). Blood samples for CD40L analysis were drawn from the arterial sheath at the beginning of the procedure (pre-stenting CD40L levels) and again 24 h after the procedure (post-stenting CD40L levels). Samples were centrifuged and frozen at
Table 1 Variables
All patients (n = 40)
Elective (n = 20)
ACS (n = 20)
P value
Age (yrs) Men Family history Smokers Diabetes mellitus Hypertension Dyslipidemia Statins use
62 ± 2 17 (42) 15 (37) 16 (40) 14 (35) 32 (80) 28 (70) 23 (57)
59 ± 3 8 (40) 7 (35) 8 (40) 6 (30) 16 (80) 14 (70) 12 (60)
65 ± 2 9 (45) 8 (40) 8 (40) 8 (40) 16 (80) 14 (70) 11 (55)
0.08 0.99 0.99 1.00 0.74 1.00 1.00 0.99
Data presented as means ± SE or frequency (%).
504
M.V. Wainstein et al. / International Journal of Cardiology 130 (2008) 503–504
Fig. 1.
−80 °C. CD40L analysis was performed by Enzyme-Linked Immunosorbent Assay (ELISA) in duplicate. Assuming a difference of 20% in CD40L levels after stent implantation between patients presenting with ACS and elective patients [8], a sample size of 38 subjects was calculated (alpha 0.05 and power of 80%). Comparison between non-parametric data, such as pre-procedure plasma CD40L levels between groups was analyzed by Wilcoxon test and presented as median ± IQA (P25–P75). Pre-and postprocedure CD40L levels were compared by two way analysis of variance for repeated measures (ANOVA) after logarithmic transformation. Forty patients were enrolled in the study. Twenty patients had stable coronary artery disease and were considered elective candidates for stent implantation, while 20 patients had non-ST-elevation ACS presentation. Baseline demographic and clinical characteristics, including age, gender, use of statins, presence of Diabetes mellitus, and dyslipidemia were well matched between groups (Table 1). Before stenting, median CD40L levels were significantly higher in the ACS group than in the stable patients (ACS 171 (range 97–412) μg/ dL; Stable 77 (32 to 165) μg/dL, P = 0.02). There was a significant reduction of CD40L levels after stenting in ACS patients (65 (21 to 146) μg/dL (P = 0.03 for group comparison),
while stable patients showed no significant change in CD40L levels after stenting (83 (26 to 197) μg/dL) (Fig. 1). Our findings were comparable to the study of Carbone et al. [9], where coronary stenting resulted in reduction of PAP-A levels, another inflammatory marker, after stenting in unstable angina patients. Since CD40L levels represent a clinical marker for vulnerable plaques, [4], our results might indicate that, once a vulnerable plaque target is correctly found, coronary stenting, despite being a local therapeutic alternative, may also help to seal a systemic response. However, the reduction of CD40L after coronary stenting may not necessarily be due to plaque sealing, rather to a reduction of the ischemic insult to the myocardium determined by the restore of coronary flow produced by stent implantation. In summary, in this prospective observational study, we found a significant reduction of CD40L levels after coronary stenting in non-ST-elevation ACS patients as compared to stable subjects. Elective candidates to coronary stent placement had a lower baseline CD40L level, and showed no significant change 24 hours after stenting. Although coronary stenting is a well-recognized cause of vessel wall injury and inflammation, this effect might be blunted by the vulnerable plaque sealing effect associated to stent implantation in ACS patients. Therefore, our findings indicate one possible mechanism for the benefits of coronary stenting as a therapeutic modality to ACS patients. References [1] Davies MJ. Stability and instability: two faces of coronary atherosclerosis. Circulation 1996;94:2013–20. [2] Davies MJ. A macro and micro view of coronary vascular insult in ischemic heart disease. Circulation 1990;82(Suppl II):II-38–46. [3] Davies MJ. The composition of coronary-artery plaques. N Engl J Med 1997;336:1312–4. [4] Andre P, Nannizzi-Alaimo L, Prasad SK, Phillips DR. Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. Circulation 2002;106:896–9. [5] Schonbeck U, Libby P. The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci 2001;58:4–43. [6] Henn V, Steinbach S, Buchner K, et al. The inflammatory action of CD40 ligand (CD154) expressed on actived humans platelets is temporally limited by coexpressed CD40. Blood 2001;98:1047–54. [7] Henn V, Slupsky J, Grafe M, et al. CD40 ligand on actived platelets triggers an inflammatory reaction of endothelial cells. Nature 1998;391:591–4. [8] Heeschen C, Dimmeler F, Hamm CW, et al. Soluble CD40 ligand in ACSs. N Engl J Med 2003;348:1104–11. [9] Carbone GL, Oxvig C, Medda M, et al. Plaque sealing with stenting is associated with marked reduction of biologic markers of vulnerability. Am J Cardiol 2003;92:5L. [10] Garlichs CD, Eskafi S, Raaz D, et al. Patients with ACSs express enhanced CD40 ligand /CD154 on platelets. Heart 2001;86:649–55.
Letter to the Editor
Coronary stent implantation may seal the inflammatory response in patients with acute coronary syndromes Marco V. Wainstein a,⁎, Diego P. Bento da Silva a , Jorge P. Ribeiro a,b a
b
Cardiology Division, Hospital de Clínicas de Porto Alegre, Brazil Department of Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil Received 1 June 2007; accepted 1 July 2007 Available online 4 October 2007
Abstract The change in CD40L levels before and 24 h coronary stenting was compared in patients presenting with acute coronary syndromes and for elective angioplasty. Baseline CD40L levels were lower in stable subjects, whereas unstable patients had a significant decrease of CD40L after stenting. This might suggest that coronary stenting, despite of being a local therapy, can help to seal a systemic inflammatory response in acute coronary syndromes. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: CD40; Stent; Acute coronary syndromes
Plaque vulnerability may involve a systemic inflammatory state which includes multiple interactions between leucocytes, endothelial cells, and platelets [1–4]. Recent data suggests that CD40L may be the cornerstone of this process [4]. CD40L is a trimetric transmembrane protein from the tumor necrosis factor family, which was originally identified in the immune system, but is also present in the endothelial and inflammatory cells, as well as in activated platelets [5,6]. The association of CD40L and platelets is capable of inducing an inflammatory response and ultimately to promote matrix degradation and plaque rupture [7]. Elevated levels of CD40L can help to identify patients with ACS that are at higher risk of cardiovascular adverse events, regardless of other markers of myocardial ischemia, such as creatine kinase-Mb and troponins [8]. Despite the fact that coronary stent implantation offers a local therapeutic alternative, it is controversial if this could lead to a systemic reduction of plaque vulnerability,[9] rather to increase the inflammatory response locally [10]. ⁎ Corresponding author. Cardiology Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350 90035-003, Porto Alegre, RS Brazil. Tel.: +55 51 9916 0826; fax: +55 51 2101 8621. E-mail address: [email protected] (M.V. Wainstein). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.07.051
We conducted a prospective, observational study. Patients of both genders, aged 18 to 75 years, referred for stent implantation were recruited. According to clinical presentation, patients were divided in two groups: stable angina and/or silent myocardial ischemia as detected on functional tests (stable); and high-risk non-ST-elevation ACS (ACS). Blood samples for CD40L analysis were drawn from the arterial sheath at the beginning of the procedure (pre-stenting CD40L levels) and again 24 h after the procedure (post-stenting CD40L levels). Samples were centrifuged and frozen at
Table 1 Variables
All patients (n = 40)
Elective (n = 20)
ACS (n = 20)
P value
Age (yrs) Men Family history Smokers Diabetes mellitus Hypertension Dyslipidemia Statins use
62 ± 2 17 (42) 15 (37) 16 (40) 14 (35) 32 (80) 28 (70) 23 (57)
59 ± 3 8 (40) 7 (35) 8 (40) 6 (30) 16 (80) 14 (70) 12 (60)
65 ± 2 9 (45) 8 (40) 8 (40) 8 (40) 16 (80) 14 (70) 11 (55)
0.08 0.99 0.99 1.00 0.74 1.00 1.00 0.99
Data presented as means ± SE or frequency (%).
504
M.V. Wainstein et al. / International Journal of Cardiology 130 (2008) 503–504
Fig. 1.
−80 °C. CD40L analysis was performed by Enzyme-Linked Immunosorbent Assay (ELISA) in duplicate. Assuming a difference of 20% in CD40L levels after stent implantation between patients presenting with ACS and elective patients [8], a sample size of 38 subjects was calculated (alpha 0.05 and power of 80%). Comparison between non-parametric data, such as pre-procedure plasma CD40L levels between groups was analyzed by Wilcoxon test and presented as median ± IQA (P25–P75). Pre-and postprocedure CD40L levels were compared by two way analysis of variance for repeated measures (ANOVA) after logarithmic transformation. Forty patients were enrolled in the study. Twenty patients had stable coronary artery disease and were considered elective candidates for stent implantation, while 20 patients had non-ST-elevation ACS presentation. Baseline demographic and clinical characteristics, including age, gender, use of statins, presence of Diabetes mellitus, and dyslipidemia were well matched between groups (Table 1). Before stenting, median CD40L levels were significantly higher in the ACS group than in the stable patients (ACS 171 (range 97–412) μg/ dL; Stable 77 (32 to 165) μg/dL, P = 0.02). There was a significant reduction of CD40L levels after stenting in ACS patients (65 (21 to 146) μg/dL (P = 0.03 for group comparison),
while stable patients showed no significant change in CD40L levels after stenting (83 (26 to 197) μg/dL) (Fig. 1). Our findings were comparable to the study of Carbone et al. [9], where coronary stenting resulted in reduction of PAP-A levels, another inflammatory marker, after stenting in unstable angina patients. Since CD40L levels represent a clinical marker for vulnerable plaques, [4], our results might indicate that, once a vulnerable plaque target is correctly found, coronary stenting, despite being a local therapeutic alternative, may also help to seal a systemic response. However, the reduction of CD40L after coronary stenting may not necessarily be due to plaque sealing, rather to a reduction of the ischemic insult to the myocardium determined by the restore of coronary flow produced by stent implantation. In summary, in this prospective observational study, we found a significant reduction of CD40L levels after coronary stenting in non-ST-elevation ACS patients as compared to stable subjects. Elective candidates to coronary stent placement had a lower baseline CD40L level, and showed no significant change 24 hours after stenting. Although coronary stenting is a well-recognized cause of vessel wall injury and inflammation, this effect might be blunted by the vulnerable plaque sealing effect associated to stent implantation in ACS patients. Therefore, our findings indicate one possible mechanism for the benefits of coronary stenting as a therapeutic modality to ACS patients. References [1] Davies MJ. Stability and instability: two faces of coronary atherosclerosis. Circulation 1996;94:2013–20. [2] Davies MJ. A macro and micro view of coronary vascular insult in ischemic heart disease. Circulation 1990;82(Suppl II):II-38–46. [3] Davies MJ. The composition of coronary-artery plaques. N Engl J Med 1997;336:1312–4. [4] Andre P, Nannizzi-Alaimo L, Prasad SK, Phillips DR. Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. Circulation 2002;106:896–9. [5] Schonbeck U, Libby P. The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci 2001;58:4–43. [6] Henn V, Steinbach S, Buchner K, et al. The inflammatory action of CD40 ligand (CD154) expressed on actived humans platelets is temporally limited by coexpressed CD40. Blood 2001;98:1047–54. [7] Henn V, Slupsky J, Grafe M, et al. CD40 ligand on actived platelets triggers an inflammatory reaction of endothelial cells. Nature 1998;391:591–4. [8] Heeschen C, Dimmeler F, Hamm CW, et al. Soluble CD40 ligand in ACSs. N Engl J Med 2003;348:1104–11. [9] Carbone GL, Oxvig C, Medda M, et al. Plaque sealing with stenting is associated with marked reduction of biologic markers of vulnerability. Am J Cardiol 2003;92:5L. [10] Garlichs CD, Eskafi S, Raaz D, et al. Patients with ACSs express enhanced CD40 ligand /CD154 on platelets. Heart 2001;86:649–55.