sirolimus and Systemic-Inflammatory-Response-Syndrome

The systematic pro-inflammatory responses after percutaneous coronary intervention with drug-eluting stents (DES) remain poorly defined. Therefore, we compared the systematic pro-inflammatory state of circulating mononuclear cells (MNCs) between DES and bare metal stent (BMS) implantation.. Patients with indications for treatment with stents were randomized in a 1:1 ratio to placement of DES or BMS. The primary endpoint was a change of pro-inflammatory state at 12 weeks post-procedure.. Thirty-six consecutive patients received DES or BMS. At 12 weeks after stent implantation, the lipid profile and high-sensitivity C-reactive protein (hs-CRP) improved significantly in both groups. The mRNA levels and plasma concentrations of interleukin-6, tumor necrosis factor-α and matrix metalloproteinase-9 were significantly elevated in the DES group, which was not observed in the BMS group. An increase in NF-κB binding activity and a decrease in PPAR-γ expression in MNCs were observed in the DES group, along with increases in IκB phosphorylation and p50 expression. However, similar changes were not observed in the BMS group.. Systematic inflammatory responses were accentuated after the patients were treated percutaneously with DES, despite their improved lipid profile and hs-CRP. These data may provide fundamental information for optimizing therapeutic strategy in the era of DES.

Topics: Analysis of Variance; C-Reactive Protein; Coronary Stenosis; Drug-Eluting Stents; Enzyme-Linked Immunosorbent Assay; Everolimus; Humans; Immunosuppressive Agents; Interleukin-4; Interleukin-6; Leukocytes, Mononuclear; Matrix Metalloproteinase 9; RNA, Messenger; Sirolimus; Stents; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

We compared the degree of systemic inflammation and its relation to the angiographic outcomes after drug-eluting stent (DES) implantations.. We implanted a single DES in 79 stable angina patients (50 men; 60.4 (9.5) years of age; sirolimus-eluting stent (SES), n = 38; paclitaxel-eluting stent (PES), n = 41). The high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were determined before and at 24 hours, 72 hours, and 4 weeks after the percutaneous coronary intervention (PCI). An angiography and intravascular ultrasound (IVUS) were performed.. The hs-CRP and IL-6 levels at baseline did not differ between the two groups. The hs-CRP increased significantly from baseline at 24 hours and 72 hours after the PCI in both groups and there was a significant increase in the IL-6 level at 24 hours after the PCI in both groups. However, there was no significant difference between the two groups in any of the hs-CRP or IL-6 measurements. At follow-up, the late lumen loss was significantly higher in the PES group than in the SES group (0.57 (0.56) mm vs 0.28 (0.58) mm, respectively, p = 0.020). The neointimal hyperplasia (NIH) volume in the PES group was significantly higher than that in the SES group (23.1 (22.7) vs 3.8 (7.1) mm(3), respectively, p = 0.000). The percentage luminal volume reduction was higher in the PES group than in the SES group (18.9 vs 3.9%, p = 0.002). The absolute values or change in the inflammatory markers did not correlate with the NIH or stent volume reduction.. Our study showed that the benefits obtained from the SES, which reduce neointimal proliferation, are not probably mediated by the attenuation of the systemic inflammatory markers hs-CRP or IL-6.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Paclitaxel; Prognosis; Prospective Studies; Sirolimus; Systemic Inflammatory Response Syndrome; Treatment Outcome; Tubulin Modulators; Ultrasonography

Systemic inflammation after percutaneous coronary intervention (PCI) identifies patients at increased risk of subsequent major adverse cardiac event. During PCI, the technique of stent implantation including direct stenting (DS) and complementary stenting (CS) is guided using both clinical and angiographic features. DS was practiced with increased frequency during PCI in an attempt to reduce both restenosis and major adverse cardiac event in the drug-eluting stent (DES) era. Impact of DS on the early inflammatory response has, however, not been investigated. We hypothesized that a direct DES implantation may attenuate the early inflammatory response compared with CS.. In this study, therefore, we prospectively select the sirolimus-eluting stent (SES) as a model of DESs, and sought to determine the early systemic inflammatory response in patients with single-vessel disease after PCI using either DS or CS techniques.. Thirty-nine patients who had single-vessel disease implanted with SES were randomly enrolled into the two groups: DS group (n=20) or CS group (n=19). The blood samples were taken before PCI, 24 and 72 h after stenting. The plasma concentrations of C-reactive protein and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay.. No significant difference in baseline clinical, angiographic, and inflammatory parameters between the two groups is observed. The plasma IL-6 levels at 24 h after stent implantation were significantly higher than that at baseline in both groups (P<0.05, respectively). Plasma IL-6 level was, however, higher in CS group than in DS group (P<0.01) and was returned to baseline levels in both groups at 72 h after stenting. Meanwhile, the plasma levels of C-reactive protein were also significant higher in CS group compared with DS group at both 24 and 72 h after stenting (P<0.05, respectively).. Taken together, our findings demonstrated that a direct SES implantation significantly attenuated the early systemic inflammatory response in patients with single-vessel disease compared with CS technique.

Topics: Adult; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Prospective Studies; Prosthesis Design; Sirolimus; Systemic Inflammatory Response Syndrome; Time Factors; Treatment Outcome; Troponin I; Up-Regulation

Inflammatory markers are elevated in acute coronary syndromes, and are also known to play a crucial role in the pathogenesis of neointimal proliferation and stent restenosis. Drug-eluting stents (DESs) have been shown to decrease stent restenosis in different studies. In this study, we aimed to investigate the effect of treatment with DESs on systemic inflammatory response in patients with unstable angina pectoris who underwent percutaneous coronary intervention (PCI). We compared plasma high-sensitivity C-reactive protein (hsCRP), human tumor necrosis factor alpha (Hu TNF-alpha), and interleukin 6 (IL-6) levels after DES (dexamethasone-eluting stent [DEXES], and sirolimuseluting stent [SES]) implantation with levels after bare metal stent (BMS) implantation. We performed PCI with a single stent in 90 patients (62 men; 59 +/- 9 years of age; n = 30 in the BMS group, n = 30 in the DEXES group, n = 30 in the SES group) who had acute coronary syndrome. Plasma hsCRP, Hu TNF-alpha, and IL-6 levels were determined before intervention and at 24 h, 48 h, and 1 week after PCI. The results were as follows. Plasma hsCRP levels at 48 h (11.19 +/- 4.54, 6.43 +/- 1.63 vs 6.23 +/- 2.69 mg/l, P = 0.001) after stent implantation were significantly higher in the BMS group than in the DES group; this effect persisted for 7 days (P = 0.001). Plasma Hu TNF-alpha levels at each time point were higher in the SES group than in the BMS and DEXES groups (P < 0.05). The time course of Hu TNF-alpha values was similar in all groups. Although IL-6 levels at baseline and at 24 and 48 h showed no statistically significant difference between the study groups, postprocedural values at 7 days were slightly statistically significant in the SES group (P = 0.045). Drug-eluting stents showed significantly lower plasma hsCRP levels after PCI compared with BMSs. This may reflect the potent effects of DESs on acute inflammatory reactions induced by PCI.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents; C-Reactive Protein; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Dexamethasone; Drug-Eluting Stents; Female; Humans; Inflammation Mediators; Interleukin-6; Male; Metals; Middle Aged; Prospective Studies; Prosthesis Design; Sirolimus; Systemic Inflammatory Response Syndrome; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha