Ação da sinvastatina na resposta inflamatória aguda após infarto agudo do miocárdio com supradesnivelamento do segmento ST / The simvastatin effect on acute inflammatory response during ST elevation myocardial infarction

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Introduction: Following ST Elevation Myocardial Infarction (STEMI), the ischemic injury motivates a local and systemic inflammatory response, which is a determinant for myocardial and vascular remodeling and for the short and medium-term mortality. Statin treatment has shown to attenuate inflammatory response in individuals with hypercholesterolemia, chronic coronary artery disease (CAD) and patients with non-ST elevation myocardial infarction (NSTEMI) or unstable angina. Nevertheless, some questions remain unanswered on this matter. Firstly, it is unknown if such anti-inflammatory effect may overwhelm the extensive necrosis area in STEMI patients; Secondly, if so, is this a dose-dependent effect?; and Thirdly, is the inflammatory response influenced by the prior use or discontinuation of statin therapy? Objectives: This study aims to evaluate: (i) if the STEMI mass is determinant for the inflammatory response during the acute phase of STEMI; (ii) if the prior use or discontinuation of simvastatin affects the inflammatory response in the acute phase of STEMI; (iii) verify the if the anti-inflammatory effect of simvastatin is dose-dependent. Methods: We evaluated 247 patients (60 11 years) admitted in the first 24 hours after STEMI. All of them were submitted to a clinic and anthropometric evaluation in admission and they were followed at in-hospital period. In all enrolled patients, blood samples were taken at admission and at the fifth day after STEMI. In a subgroup of consecutive patients, blood samples were daily taken for seven days in order to determine the plasma C-reactive protein (CRP) kinetics. This subgroup was also submitted to nuclear magnetic resonance imaging (MRI) with late enhancement technique to determine the size of the STEMI area. Results: We found a weak but significant correlation between the CRP variation from admission to the fifth day after STEMI and the peak CK-MB (r=0,19; p=0,005). We did not find correlation between STEMI mass and CRP change in the subgroup of patients submitted to MRI (n=40). Patients were classified in four groups: those who were using statins prior to and during MI (SS), statins prior to but not during MI (SN), no statin prior to but during MI (NS), and no statin prior to nor during MI (NN). At baseline, statin users presented a trend to lower CRP values as compared with those without this treatment before the MI (NN: 1.0(0.4-1.5) vs NS: 1.0(0.3-2.8) vs SS: 0.5(0.3-1.0) vs SN: 0.6 (0.4-1.0) mg/dL; p=0.08). By the fifth day, CRP was significantly higher in the SN (18.1(16.1-23.2) mg/dL) group as compared with other groups (NN: 10.5(9.3-13.2) vs NS: 2.9(1.5-4.5) vs SS: 1.1(0.8-2.4) mg/dL; p<0.0001). At the fifth day, CRP in the NN group was lower than in the SN group (p<0.0001), but higher than the NS and SS groups (p<0.0001). In the dose-response analysis, plasma CRP levels at admission did not differ significantly between patients at different simvastatin doses. As of the second day of treatment, however, a statistically significant difference was found between each group by a comparative point-to-point analysis (p<0.0001). Statistical analysis of the area under the curve values revealed significant differences between groups (77 9 vs. 47 21 vs. 27 22 vs. 6 5, for non-statin users, users of 20mg/day, 40mg/day and 80mg/day, respectively; p<0.0001). This effect was equally observed when we considered the CRP variation between the admission and the fifth day in all subjects enrolled (6,8 5,2 vs. 5,7 6,5 vs 3,9 4,3 vs. 2,2 4,3; for non statin users, 20mg/ day, 40mg/ day and 80mg/ day users respectively; p<0.001). Conclusion: The systemic inflammatory response, estimated by plasma levels of CRP, is either little or not influenced by myocardial infarction extension inferred by either CK-MB peak or MRI. The statin withdrawal during acute phase STEMI provokes a rebound inflammatory effect. In contrast, prior use of statin magnifies the attenuation of the inflammatory response. The CRP reduction was significantly distinct and proportional to the simvastatin dose.

ASSUNTO(S)

infarto do miocárdio proteína c reativa de alta sensibilidade c reactive protein inflamação medicina inflammation myocardial infarction statins estatinas

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