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High sensitive C-reactive protein and interleukin 6 are not related to neointimal hyperplasia in paclitaxel eluting stents or bare metal stents. An intravascular ultrasound study
International Journal of Cardiology 119 (2007) 114 – 116 www.elsevier.com/locate/ijcard
Letter to the editor
High sensitive C-reactive protein and interleukin 6 are not related to neointimal hyperplasia in paclitaxel eluting stents or bare metal stents. An intravascular ultrasound study Jakob Klitkou ⁎, Lisette Okkels Jensen, Henrik Steen Hansen, Per Thayssen Department of Cardiology, Odense University Hospital, Odense, Denmark Received 22 March 2006; accepted 15 July 2006 Available online 25 October 2006
Abstract Implantation of coronary stents after percutaneous coronary intervention (PCI) may result in an inflammatory response with an increase in high sensitive C-reactive protein (Hs-CRP) and interleukin 6 (IL-6). In 25 patients Hs-CRP and IL-6 increased after coronary artery stenting, however, the increase in the inflammatory response did not differ between PES and BMS stents. The inflammatory response did not predict neointima hyperplasia measured by intravascular ultrasound after 6 months. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Drug eluting stent; Restenosis; Inflammation; High-sensitivity CRP; Interleukin 6; Intravascular Ultrasound
Implantation of bare metal stents (BMS) results in an inflammatory response with an increase in high sensitive Creactive protein (Hs-CRP) and interleukin 6 (IL-6). The influence of paclitaxel eluting stent (PES) on inflammatory markers after percutaneous coronary intervention (PCI) has not previously been studied [1–5]. We studied whether patients receiving a PES have a different inflammatory response after PCI compared to BMS and if these inflammatory markers predict the degree of neointimal hyperplasia (NIH) and instent lumen reduction measured by intravascular ultrasound (IVUS) after coronary stenting. 25 non-diabetic patients referred to elective PCI were randomized to either a PES or a BMS with identical design. IVUS was performed after stent implantation and at six month follow up. A 40 MHz IVUS catheter (Boston Scientfic) was advanced N 10 mm beyond the stent. An imagine run with an ⁎ Corresponding author. Departments of Cardiology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Tel.: +45 6541 2691; fax: +45 6312 1730. E-mail address: [email protected] (J. Klitkou). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.07.073
Fig. 1. Level of inflammation before and after coronary stenting measured by Hs-CRP. ⁎p b 0.05 value vs. pre.
J. Klitkou et al. / International Journal of Cardiology 119 (2007) 114–116
Fig. 2. Level of inflammation before and after coronary stenting measured by IL-6. ⁎p b 0.05 value vs. pre.
automated transducer pullback at 0.5 mm/s was performed to a point N10 mm proximal to the stent. Lumen and stent cross-sectional areas (CSA) were measured every 0.5 mm. NIH was defined as stent CSA — lumen CSA and instent lumen reduction as NIH volume/stent volume ⁎ 100. Before PCI and 2, 6, 24 h and 4 weeks after PCI blood samples were collected from all patients for measuring the inflammatory markers Hs-CRP and IL-6. All samples were taken by standard venous puncture. 1. Results The two groups did not differ in baseline characteristics. Hs-CRP increased significantly from baseline to 24 h in both groups (Fig. 1). There was a significant rise in IL-6 after 6 and 24 h in the PES group and after 2, 6 and 24 h in the BMS
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group compared to baseline (Fig. 2). There was no significant difference between the two groups in any of the Hs-CRP and IL-6 measurements. 3 patients had more than one stent implanted (1 in the PES group and 2 in the BMS group). For the 2 patients in the BMS group the stents were placed end to end and is analyzed as being one stent in the 3D IVUS analysis. After PCI the proximal lumen CSA was significant larger in the PES group (9.8 mm2) than in the BMS group (6.7 mm2) ( p = 0.044). There was no significant difference in lumen CSA in any of the other segments. At follow up the degree of NIH in the PES group was 0.7 mm2 vs. 1.5 mm2 in the BMS group, p = 0.05. Instent lumen reduction was significantly lower in the PES group compared to the BMS group 7.9% vs. 21.3%, p = 0.007 (Figs. 3 and 4). At follow up proximal lumen CSA was significant lower in the BMS group 5.9 mm2 vs. 9.4 mm2 compared to the PES group ( p = 0.035). Also stent lumen CSA was significant lower in the BMS group (4.5 mm2) compared to the PES group (6.9 mm2) ( p = 0.046). In the BMS group stent lumen CSA was significant lower at follow up compared to baseline 6.1 mm2 vs. 4.5 mm2 respectively ( p = 0.002). The absolute values or changes in inflammatory markers did not correlate to NIH or stent lumen reduction. 2. Comments PCI with coronary stenting resulted in an inflammatory response measured as an increase in Hs-CRP and IL-6. This inflammatory response did not differ between patients treated with a PES or a BMS in the present study. The inflammatory response was not related to NIH or lumen reduction, neither in the stent nor in the reference segments. These results are in agreement with the inflammatory markers on angiographic restenosis [5]. However, Hong et al. [6] have shown a significant correlation between pre-procedural Hs-CRP and NIH (r = 0.52, p b 0.001) and restenosis rates
Fig. 3. Left hand side shows instent lumen reduction at follow up. Right hand side shows NIH at follow up.
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Fig. 4. The top left panel illustrates a cross-section intravascular ultrasound examination at baseline in a patient receiving a PES, while the top right panel shows the same cross-section at 6 months follow up. The bottom left panel illustrates a cross-section in a patient receiving a BMS and the bottom right panel shows the same patient at 6 months follow up.
evaluated by IVUS. The two patient populations are not comparable as patients with stable angina, unstable angina, non-ST elevation myocardial infarction and ST elevation myocardial infarction were included in the other study, and all patients were treated with BMS. The majority of studies looking at acute-phase reactants and outcome are using a clinical follow up rather than angiographic or IVUS parameters. Buffon et al. [1] found that patients with a high baseline CRP were more likely to experience clinical restenosis at one year follow up after angioplasty than patients with low baseline CRP ( p b 0.001). Clinical restenosis was defined as recurrence or worsening of ischemic symptoms or ischemia at exercise testing. In a study of 483 patients there were found a significant association between level of CRP at baseline and risk for recurrence of symptoms at one year follow up. However, the same study did not show any significant association between baseline CRP and angiographic instent restenosis at follow up [4]. A reason for these results may be that a high baseline level of CRP indicate that these patients have several vulnerable plaques rather that a single vulnerable lesion.
References [1] Buffon A, Liuzzo G, Biasucci LM, et al. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999;34: 1512–21. [2] Rahel BM, Visseren FLJ, Suttorp MJ, et al. Preprocedural serum levels of acute-phase reactants and prognosis after percutaneous coronary intervention. Cardiovasc Res 2002;60: 136–40. [3] 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 percutanous coronary intervention. Am Heart J 2002;144: 491–500. [4] 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. [5] Segev A, Kassam S, Buller CE, 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. [6] Hong YJ, Jeong MH, Lim SY, et al. Elevated preprocedural highsensitivity C-reactive protein levels are associated with neointimal hyperplasia and restenosis development after successful coronary artery stenting. Circ J 2005;69: 1477–83.
Letter to the editor
High sensitive C-reactive protein and interleukin 6 are not related to neointimal hyperplasia in paclitaxel eluting stents or bare metal stents. An intravascular ultrasound study Jakob Klitkou ⁎, Lisette Okkels Jensen, Henrik Steen Hansen, Per Thayssen Department of Cardiology, Odense University Hospital, Odense, Denmark Received 22 March 2006; accepted 15 July 2006 Available online 25 October 2006
Abstract Implantation of coronary stents after percutaneous coronary intervention (PCI) may result in an inflammatory response with an increase in high sensitive C-reactive protein (Hs-CRP) and interleukin 6 (IL-6). In 25 patients Hs-CRP and IL-6 increased after coronary artery stenting, however, the increase in the inflammatory response did not differ between PES and BMS stents. The inflammatory response did not predict neointima hyperplasia measured by intravascular ultrasound after 6 months. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Drug eluting stent; Restenosis; Inflammation; High-sensitivity CRP; Interleukin 6; Intravascular Ultrasound
Implantation of bare metal stents (BMS) results in an inflammatory response with an increase in high sensitive Creactive protein (Hs-CRP) and interleukin 6 (IL-6). The influence of paclitaxel eluting stent (PES) on inflammatory markers after percutaneous coronary intervention (PCI) has not previously been studied [1–5]. We studied whether patients receiving a PES have a different inflammatory response after PCI compared to BMS and if these inflammatory markers predict the degree of neointimal hyperplasia (NIH) and instent lumen reduction measured by intravascular ultrasound (IVUS) after coronary stenting. 25 non-diabetic patients referred to elective PCI were randomized to either a PES or a BMS with identical design. IVUS was performed after stent implantation and at six month follow up. A 40 MHz IVUS catheter (Boston Scientfic) was advanced N 10 mm beyond the stent. An imagine run with an ⁎ Corresponding author. Departments of Cardiology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Tel.: +45 6541 2691; fax: +45 6312 1730. E-mail address: [email protected] (J. Klitkou). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.07.073
Fig. 1. Level of inflammation before and after coronary stenting measured by Hs-CRP. ⁎p b 0.05 value vs. pre.
J. Klitkou et al. / International Journal of Cardiology 119 (2007) 114–116
Fig. 2. Level of inflammation before and after coronary stenting measured by IL-6. ⁎p b 0.05 value vs. pre.
automated transducer pullback at 0.5 mm/s was performed to a point N10 mm proximal to the stent. Lumen and stent cross-sectional areas (CSA) were measured every 0.5 mm. NIH was defined as stent CSA — lumen CSA and instent lumen reduction as NIH volume/stent volume ⁎ 100. Before PCI and 2, 6, 24 h and 4 weeks after PCI blood samples were collected from all patients for measuring the inflammatory markers Hs-CRP and IL-6. All samples were taken by standard venous puncture. 1. Results The two groups did not differ in baseline characteristics. Hs-CRP increased significantly from baseline to 24 h in both groups (Fig. 1). There was a significant rise in IL-6 after 6 and 24 h in the PES group and after 2, 6 and 24 h in the BMS
115
group compared to baseline (Fig. 2). There was no significant difference between the two groups in any of the Hs-CRP and IL-6 measurements. 3 patients had more than one stent implanted (1 in the PES group and 2 in the BMS group). For the 2 patients in the BMS group the stents were placed end to end and is analyzed as being one stent in the 3D IVUS analysis. After PCI the proximal lumen CSA was significant larger in the PES group (9.8 mm2) than in the BMS group (6.7 mm2) ( p = 0.044). There was no significant difference in lumen CSA in any of the other segments. At follow up the degree of NIH in the PES group was 0.7 mm2 vs. 1.5 mm2 in the BMS group, p = 0.05. Instent lumen reduction was significantly lower in the PES group compared to the BMS group 7.9% vs. 21.3%, p = 0.007 (Figs. 3 and 4). At follow up proximal lumen CSA was significant lower in the BMS group 5.9 mm2 vs. 9.4 mm2 compared to the PES group ( p = 0.035). Also stent lumen CSA was significant lower in the BMS group (4.5 mm2) compared to the PES group (6.9 mm2) ( p = 0.046). In the BMS group stent lumen CSA was significant lower at follow up compared to baseline 6.1 mm2 vs. 4.5 mm2 respectively ( p = 0.002). The absolute values or changes in inflammatory markers did not correlate to NIH or stent lumen reduction. 2. Comments PCI with coronary stenting resulted in an inflammatory response measured as an increase in Hs-CRP and IL-6. This inflammatory response did not differ between patients treated with a PES or a BMS in the present study. The inflammatory response was not related to NIH or lumen reduction, neither in the stent nor in the reference segments. These results are in agreement with the inflammatory markers on angiographic restenosis [5]. However, Hong et al. [6] have shown a significant correlation between pre-procedural Hs-CRP and NIH (r = 0.52, p b 0.001) and restenosis rates
Fig. 3. Left hand side shows instent lumen reduction at follow up. Right hand side shows NIH at follow up.
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J. Klitkou et al. / International Journal of Cardiology 119 (2007) 114–116
Fig. 4. The top left panel illustrates a cross-section intravascular ultrasound examination at baseline in a patient receiving a PES, while the top right panel shows the same cross-section at 6 months follow up. The bottom left panel illustrates a cross-section in a patient receiving a BMS and the bottom right panel shows the same patient at 6 months follow up.
evaluated by IVUS. The two patient populations are not comparable as patients with stable angina, unstable angina, non-ST elevation myocardial infarction and ST elevation myocardial infarction were included in the other study, and all patients were treated with BMS. The majority of studies looking at acute-phase reactants and outcome are using a clinical follow up rather than angiographic or IVUS parameters. Buffon et al. [1] found that patients with a high baseline CRP were more likely to experience clinical restenosis at one year follow up after angioplasty than patients with low baseline CRP ( p b 0.001). Clinical restenosis was defined as recurrence or worsening of ischemic symptoms or ischemia at exercise testing. In a study of 483 patients there were found a significant association between level of CRP at baseline and risk for recurrence of symptoms at one year follow up. However, the same study did not show any significant association between baseline CRP and angiographic instent restenosis at follow up [4]. A reason for these results may be that a high baseline level of CRP indicate that these patients have several vulnerable plaques rather that a single vulnerable lesion.
References [1] Buffon A, Liuzzo G, Biasucci LM, et al. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999;34: 1512–21. [2] Rahel BM, Visseren FLJ, Suttorp MJ, et al. Preprocedural serum levels of acute-phase reactants and prognosis after percutaneous coronary intervention. Cardiovasc Res 2002;60: 136–40. [3] 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 percutanous coronary intervention. Am Heart J 2002;144: 491–500. [4] 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. [5] Segev A, Kassam S, Buller CE, 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. [6] Hong YJ, Jeong MH, Lim SY, et al. Elevated preprocedural highsensitivity C-reactive protein levels are associated with neointimal hyperplasia and restenosis development after successful coronary artery stenting. Circ J 2005;69: 1477–83.