Author + information
- Juliano Slhessarenko1,
- Jose Costa Jr.2,
- Mario Hirata3,
- Alexandre Abizaid2,
- Renata Slhessarenko4,
- Elisa Mieko Higa5 and
- José Eduardo Souza6
Preliminary studies have shown that after initial injury with balloon catheter and/or metallic stents,there is endothelial denudation,dissection,platelet deposition and leukocyte attraction as an immediate response,which might limit the late benefits of PCI.Local injury to the arterial wall after stent implantation may promote the gene expression and release of inflammatory mediators which are directly related to the prognosis of cardiovascular disease.Despite their importance, there are few studies that characterize the acute inflammatory response after coronary stent implantation and correlate it to the occurrence of adverse events.Objectives:We sougth to evaluate the effects of the loading dose of Rosuvastatin (40mg) on the acute inflammatory response after PCI with mettalic stents, as well as to correlate the variations in cytokine levels and their respective gene expression.
Patients with stable coronary disease without statin(≥7 days) undergoing elective PCI to de novo lesions in the native coronary artery were randomized to receive a loading dose of 40 mg of rosuvastatin[N = 63] versus a control group(CG) (absence of loading dose);[N = 61].Blood samples were obtained prior to oral administration of the statin (A),03 hours after medication (B) and 03 hours after PCI (C).The following laboratory tests were conducted: complete blood count,C-reactive protein (CRP),nitric oxide (NO) and analysis of gene and protein expression by means of RT-qPCR and multiplex luminex,IL-1 mediators,IL-6,IL-8, PAI-1,MCP-1,TNF-α and TGF-β.Clinical follow up was achieved up to 12 months after the procedure.
The groups did not significantly differ regarding clinical,angiographic and procedure characteristics,except for the higher amount of bifurcation lesions in the CG (19.7% versus 6.2%, p = 0.032).Among patients pre treated with the statin,there was a reduction in gene expression for IL-6(p <0.001), IL-1β(p = 0.016) and PAI-1(p = 0.002).For the IL analyses, a progressive decrease in the concentrations of IL-6 0.209 pg/ml (IC 0.156; 0.28 p <0.001), IL-1β 0.491 pg/ml (IC 0.349; 0.692, p<0.001) and PAI-1 0.986 pg/ml with paving <0.001) were observed among patients treated with the statin.Furthermore,a progressive reduction in the concentration of CRP was observed in the three timepoints among patients of the rosuvastatin cohort (p=0.04). An increase in NO concentration was observed from timepoint A to C in the statin group(p=0.004). During the in hospital period, more periprocedural MI occurred among patients in the control group(23%vs4.7%, p=0.004). Also,12-month MACE rate was higher in the control group (9.8%vs1.6%, p=0.058).
Pre-loading with high dose of rosuvastatin resulted in a marked reduction in the expression of the main inflammatory markers (IL-1β,IL-6,PAI-1 and CRP) associated with restenosis after PCI with stents.Additionally,an increase in the NO blood concentration was noticed among these patients.
CORONARY: Cell Therapy and Angiogenesis