Esquemas terapêuticos com antiplaquetários e hipolipemiantes na modulação da resposta humoral anti-fragmentos da apolipoproteína B
Data
2022-07-07
Autores
Vera, Daphnne Camaroske 
Orientadores
Fonseca, Henrique Andrade Rodrigues da
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: Investigar a modulação da resposta humoral anti- ApoB-A e anti- ApoB-D, peptídeos derivados da sequência proteica da ApoB se alteram após o manejo farmacológico com a combinação entre antiplaquetários e estatinas em pacientes após um IAMCST. Materiais e Métodos: Estudo clínico, randomizado 1:1:1:1, aberto, grupos paralelos com avaliação cega dos desfechos. Os pacientes foram randomizados para os seguintes braços terapêuticos: 1. clopidogrel 75 mg + rosuvastatina 20 mg – 2. clopidogrel 75 mg + sinvastatina 40 mg – 3. Ticagrelor 180 mg + sinvastatina 40 mg – 4. Ticagrelor 180 mg + rosuvastatina 20 mg. Foram incluídos 138 pacientes após um infarto agudo do miocárdio com supra desnivelamento do segmento ST documentado. As amostras biológicas foram coletadas em 12 horas de jejum em três visitas ao longo do seguimento (dia inicial, 30 dias após a randomização e 180 dias após a randomização). As amostras foram armazenadas em -80º e analisadas em conjunto para avaliação dos títulos de autoanticorpos IgG e IgM do anti-ApoB-A e IgG e IgM do anti-ApoB-D pelo método de ELISA. Foram avaliados os níveis plasmáticos de Troponina I (4ª geração), por imunoensaio de micropartículas CRPus por turbidimetria e paratormônio (PTH) usando imunoensaio de eletroquimioluminescência. Uma sub-amostra realizou exame de ressonância magnética (RM) cardíaca no 30º dia após infarto do miocárdio, relatando alterações entre os 30 e 180 dias. Os dados foram processados e analisados através do software Statistical Package Social Sciences (SPSS) para Windows, versão 13.0. Para todos os testes foram adotados valores significantes quando valores de p ≤ 0,05. Resultados: As combinações terapêuticas ao longo seguimento não apresentaram modulações da resposta imune humoral anti-ApoB-A e ApoB-D. Observamos que a resposta humoral natural IgM anti-ApoB-A foi modulada pela combinação rosuvastatina e clopidogrel ao longo do seguimento. Demais respostas humorais não foram alteradas em relação a idade e gênero. Os achados da avaliação de subgrupo de paciente que realizaram RM, revelaram os resultados de área de massa infartada não revelaram associação com a resposta imune, porémas concentrações de PTH plasmático apresentaram correlação com os títulos de IgG anti-ApoB-D e anti-ApoB-A referentes a visita de 180 dias.
Conclusão: O presente estudo não observou modulação da resposta humoral anti-peptídeos derivados da ApoB em nenhuma das combinações terapêuticas adotadas ao logo do seguimento, bem como em relação a função cardíaca, sexo ou idade. Contudo, os níveis circulantes de PTH apresentaram correlação positiva com os títulos de IgG anti-ApoB-A e ApoB-D.
Investigating the modulation of the anti-ApoB-A and anti-ApoB-D humoral response, peptides results from the protein sequence of ApoB changes after pharmacological management with an antiplatelet and statins in patients with an STEMI. Materials and Methods: Clinical study, randomized 1:1:1:1, open, parallel groups with final blind outcome. Patients were randomized to the following therapeutic arms: 1. clopidogrel 75 mg + rosuvastatin 20 mg – 2. clopidogrel 75 mg + simvastatin 40 mg – 3. Ticagrelor 180 mg + simvastatin 40 mg – 4. Ticagrelor 180 mg + rosuvastatin 20 mg. We included 138 patients who suffered an acute myocardial infarction with documented ST-segment elevation. Biological samples of 12 hours of fasting were collected from patients at 3 different times (initial day, 30 days after the start of treatment and 180 days after the start of treatment). The samples were stored at -80º and analyzed together to validate the titers of autoantibodies IgG and IgM of anti- ApoB-A and IgG and IgM of anti-ApoB-D by the method of ELISA. Plasma levels of Troponin I (4th generation) were evaluated by turbidimetry and parathyroid hormone (PTH) CRPus microparticle immunoassay using electrochemiluminescence immunoassay. A subsample underwent cardiac magnetic resonance imaging (MRI) on the 30th day after STEMI, reporting changes between 30 and 180 days. The data were processed and analyzed using the Statistical Package Social Sciences (SPSS) software for Windows, version 13.0. For all tests, significant values were adopted when p values ≤ 0.05. Results: The therapeutic combinations during the long follow-up showed no modulations of the anti-ApoB-A and ApoB-D humoral immune response. We observed that the natural IgM anti- ApoB-A humoral response was modulated by the combination of rosuvastatin and clopidogrel throughout follow-up. Other humoral responses were not altered in relation to age and gender. The findings of the evaluation of a subgroup of patients who underwent MRI, revealed the results of infarcted mass area, did not reveal an association with the immune response, but plasma PTH concentrations correlated with anti-ApoB-D and anti-ApoB IgG titers. -A referring to the visit of 180 days. Conclusion: The present study did not observe any modulation of the humoral response to anti-ApoB derived peptides in any of the therapeutic combinations adopted during the follow-up period, as well as in relation to cardiac function, sex or age. However, circulating PTH levels were positively correlated with anti-ApoB- A and ApoB-D IgG titers.
Investigating the modulation of the anti-ApoB-A and anti-ApoB-D humoral response, peptides results from the protein sequence of ApoB changes after pharmacological management with an antiplatelet and statins in patients with an STEMI. Materials and Methods: Clinical study, randomized 1:1:1:1, open, parallel groups with final blind outcome. Patients were randomized to the following therapeutic arms: 1. clopidogrel 75 mg + rosuvastatin 20 mg – 2. clopidogrel 75 mg + simvastatin 40 mg – 3. Ticagrelor 180 mg + simvastatin 40 mg – 4. Ticagrelor 180 mg + rosuvastatin 20 mg. We included 138 patients who suffered an acute myocardial infarction with documented ST-segment elevation. Biological samples of 12 hours of fasting were collected from patients at 3 different times (initial day, 30 days after the start of treatment and 180 days after the start of treatment). The samples were stored at -80º and analyzed together to validate the titers of autoantibodies IgG and IgM of anti- ApoB-A and IgG and IgM of anti-ApoB-D by the method of ELISA. Plasma levels of Troponin I (4th generation) were evaluated by turbidimetry and parathyroid hormone (PTH) CRPus microparticle immunoassay using electrochemiluminescence immunoassay. A subsample underwent cardiac magnetic resonance imaging (MRI) on the 30th day after STEMI, reporting changes between 30 and 180 days. The data were processed and analyzed using the Statistical Package Social Sciences (SPSS) software for Windows, version 13.0. For all tests, significant values were adopted when p values ≤ 0.05. Results: The therapeutic combinations during the long follow-up showed no modulations of the anti-ApoB-A and ApoB-D humoral immune response. We observed that the natural IgM anti- ApoB-A humoral response was modulated by the combination of rosuvastatin and clopidogrel throughout follow-up. Other humoral responses were not altered in relation to age and gender. The findings of the evaluation of a subgroup of patients who underwent MRI, revealed the results of infarcted mass area, did not reveal an association with the immune response, but plasma PTH concentrations correlated with anti-ApoB-D and anti-ApoB IgG titers. -A referring to the visit of 180 days. Conclusion: The present study did not observe any modulation of the humoral response to anti-ApoB derived peptides in any of the therapeutic combinations adopted during the follow-up period, as well as in relation to cardiac function, sex or age. However, circulating PTH levels were positively correlated with anti-ApoB- A and ApoB-D IgG titers.