Genética e Toma de Estatinas na Progressão da Degenerescência Macular da Idade

Autores

  • Maria Luz Cachulo AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal; Ophthalmology Department, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Faculty of Medicine; University of Coimbra, Coimbra, Portugal https://orcid.org/0000-0002-0900-4548
  • Cláudia Farinha AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal;  Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Centre for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Ophthalmology Department, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Faculty of Medicine; University of Coimbra, Coimbra, Portugal https://orcid.org/0000-0003-4596-0913
  • Rita Coimbra AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal https://orcid.org/0000-0002-3977-4164
  • Joana Barbosa Melo Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Centre for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Cytogenetics and Genomics Laboratory, Clinical Academic Center of Coimbra (CACC), Faculty of Medicine; University of Coimbra, Coimbra, Portugal; Univ Coimbra, Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra, Portugal https://orcid.org/0000-0001-5049-2670
  • José Cunha-Vaz AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal https://orcid.org/0000-0002-0947-9850
  • Rufino Silva AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal;  Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Centre for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Ophthalmology Department, Hospitais da Universidade de Coimbra, Unidade Local de Saúde de Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Faculty of Medicine; University of Coimbra, Coimbra, Portugal https://orcid.org/0000-0001-8676-0833
  • Patrícia Barreto AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Centre for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal https://orcid.org/0000-0002-3375-551X

DOI:

https://doi.org/10.48560/rspo.33192

Palavras-chave:

Degenerescência Macular/genética, Inibidores da Hidroximetilglutaril-CoA Redutase, Predisposição Genética para a Doença, Progressão da Doença

Resumo

INTRODUÇÃO: A degenerescência macular da idade (DMI) é uma doença multifactorial cuja fisiopatologia permanece inconclusiva. O metabolismo lipídico é um dos mecanismos identificados. Os drusen, característicos da doença, são ricos em lípidos. Adicionalmente, estão associados à doença genes da homeostase lipídica. As estatinas são fármacos estudados como alvo terapêutico, embora sem resultados conclusivos. O nosso objectivo é avaliar se as estatinas são protectoras da progressão da DMI, considerando o risco genético para a doença.
MATERIAL E MÉTODOS: Seiscentos oitenta três participantes (1321 olhos): 112 progressores ao longo de 6,5 anos (168 olhos) e 561 não progresores (1153 olhos). Os progressores progrediram do nível 0, 1a ou 1b para os níveis 2,3 e 4 entre visitas do Coimbra Eye Study (Classificação de Roterdão). Foram apenas considerados os participantes que tomaram estatinas entre as visitas. O risco genético foi calculado com os 52 SNPs. Definiu-se a potência das estatinas de acordo com guidelines do INFARMED. Calculou-se a associação entre as estatinas e a progressão da DMI usando uma extensão do modelo de regressão de COX, ajustado à baseline para a idade, sexo, IMC, tabaco, diabetes e pressão arterial. A toma de estatinas foi corrigida pelo risco genético. Considerou-se a correlação entre olhos.
RESULTADOS: A associação entre as estatinas e risco diminuído de progressão da DMI foi estatisticamente significativa (HR=0,509, 95% CI 0,302-0,860, p=0,012), ajustada à baseline para a idade, sexo, IMC, tabaco, diabetes e pressão arterial. Esta associação manteve-se para as estatinas de alta e média potência (HR=0,482, 95% CI 0,285-0,814, p=0,006), mas não para as de baixa potência (HR=1,321, 95% CI 0,159-10,995, p=0,797). A associação à diminuição do risco de progressão manteve-se significativa depois de ajustada ao risco genético para a DMI (HR=0,516, 95% CI 0,293-0,91, p=0,022).
CONCLUSÃO: A toma de estatinas sugeriu uma protecção contra a progressão da DMI, mesmo considerando o risco genético para a doença, evidenciando o envolvimento lipídico na sua fisiopatologia. Estes resultados indicam que as estatinas podem ser benéficas na gestão da doença, mesmo ponderando o perfil genético da DMI, contribuindo para uma possível estratégia terapêutica.

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Publicado

2024-10-26

Como Citar

Cachulo, M. L., Farinha, C., Coimbra, R., Barbosa Melo, J., Cunha-Vaz, J., Silva, R., & Barreto, P. (2024). Genética e Toma de Estatinas na Progressão da Degenerescência Macular da Idade. Revista Sociedade Portuguesa De Oftalmologia. https://doi.org/10.48560/rspo.33192

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