Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC Sc9CFncKS7BJFPrKMjZ6T7J S0066-782X2020000300476 abc.20200033 10.36660/abc.20200033 Minieditorial Discordância da Lipoproteína de Baixa Densidade e da Lipoproteína de Alta Densidade com Gravidade de Doença Arterial Coronariana 0000-0001-5123-3080 Castro Iran 1 Fontana Hugo Filho 1 Instituto de Cardiologia Fundação Universitária de Cardiologia Porto Alegre RS Brasil Instituto de Cardiologia - Fundação Universitária de Cardiologia,Porto Alegre, RS - Brasil Correspondência: Iran Castro • Instituto de Cardiologia - Métodos Gráficos - Av. Princesa Isabel, 395. CEP 90620-000, Santana, Porto Alegre, RS – Brasil E-mail: irancstro@gmail.com 06 04 2020 May-Jun 2020 114 3 476 476 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Doenças Cardiovasculares/mortalidade Lipoproteinas LDL Lipoproteinas HDL Doença da Artéria Coronariana Inibidores de Hidroximetilglutaril-CoA Redutases Pro-Proteina Convertase 9

As doenças cardiovasculares (DCVs) são as principais causas de morte em todo o mundo.1 A dislipidemia é um fator de risco e também um fator causal de DCVs, sendo foco da terapia de prevenção primária e secundária das DCVs.

Existe um consenso e um amplo conhecimento acerca dos mecanismos causais da lipoproteína de baixa densidade (LDL) nas DCVs, e os benefícios da terapia hipolipemiante, sendo que a magnitude de seu efeito é proporcional à redução dos níveis circulantes.2 No entanto, apesar do uso intensivo de agentes hipolipemiantes, permanece um risco residual, um alvo constante de pesquisa e terapia.

Evidência recente confirma que o evento inicial da aterogênese é a retenção de LDL e outras partículas na parede do vaso.3 Níveis elevados de colesterol não-HDL ajudam a identificar pacientes que continuam com alto risco para eventos cardiovasculares apesar de níveis baixos de LDL.4

O presente estudo5 avaliou retrospectivamente características anatômicas de 574 pacientes diagnosticados com síndrome coronariana aguda e correlacionou os achados com níveis séricos de LDL e não-HDL. Observou-se uma discordância de 15% entre LDL e não-HDL, o que foi similar a estudos prévios.6 No entanto, não foram identificadas diferenças anatômicas significativas na avaliação da gravidade da doença aterosclerótica. O uso prévio de estatinas tem um efeito mais significativo na redução de LDL em comparação a não-HDL, o que pode explicar a falta de associação.

Além disso, a sensibilidade dos níveis de LDL em identificar risco cardiovascular é menor no diabetes.7 De fato, o presente estudo identificou discrepâncias na associação entre diabetes mellitus e níveis de LDL. Talvez o tamanho da amostra não tenha sido adequado para identificar diferenças anatômicas entre os grupos. O acompanhamento de pacientes com associações discrepantes poderia identificar um subgrupo de pacientes em alto risco para novos eventos cardiovasculares.

As diretrizes brasileiras já incluem metas de LDL e não-HDL, buscando identificar indivíduos com níveis adequados de LDL e alto risco residual para eventos cardiovasculares. Estudos prospectivos certamente ajudarão a identificar o subgrupo de pacientes que requeiram uma abordagem terapêutica mais intensa, e que provavelmente se beneficiariam de terapias mais caras e efetivas, como inibidores de PCSK9 e lomitapida.8 Estudos anteriores já mostraram a eficácia desses medicamentos na redução de eventos cardiovasculares e apolipoprotein(a) em alguns grupos de pacientes.

Referências 1. Organização Mundial da Saúde; Organização Pan-Americana da Saúde. (OPAS/OMS) [Internet]. Doenças cardiovasculares. (acesso em 2020 jan 11). Disponível em: <https://www.paho.org/bra/index.php?option=com_content&view=article&id=5638:10-principais-causas-de-morte-no-mundo&Itemid=0 Organização Mundial da Saúde Organização Pan-Americana da Saúde Internet Doenças cardiovasculares acesso em 2020 jan 11 https://www.paho.org/bra/index.php?option=com_content&view=article&id=5638:10-principais-causas-de-morte-no-mundo&Itemid=0 2. Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016;316(12):1289. Silverman MG Ference BA Im K Wiviott SD Giugliano RP Grundy SM et al Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis JAMA 2016 316 12 1289 3. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Lowdensity lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459-72. Ference BA Ginsberg HN Graham I Ray KK Packard CJ Bruckert E et al Lowdensity lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel Eur Heart J 2017 38 32 2459 2472 4. Arsenault BJ, Boekholdt SM, Kastelein JJ. Lipid parameters for measuring risk of cardiovascular disease. Nat Rev Cardiol. 2011;8(4):197-206. Arsenault BJ Boekholdt SM Kastelein JJ Lipid parameters for measuring risk of cardiovascular disease Nat Rev Cardiol 2011 8 4 197 206 5. Kurmus O, Erkan AF, Ekici B, Aslan T, Eren M. Discordance of Low-Density Lipoprotein Cholestrol and Non-High-Density Lipoprotein Cholestrol and Coronary Artery Disease Severity. Arq Bras Cardiol. 2020; 114(3):469-475 Kurmus O Erkan AF Ekici B Aslan T Eren M Discordance of Low-Density Lipoprotein Cholestrol and Non-High-Density Lipoprotein Cholestrol and Coronary Artery Disease Severity Arq Bras Cardiol 2020 114 3 469 475 6. Sniderman AD, Islam S, Yusuf S, McQueen MJ. Discordance analysis of apolipoprotein B and non-high density lipoprotein cholesterol as markers of cardiovascular risk in the INTERHEART study. Atherosclerosis. 2012;225(2):444-9. Sniderman AD Islam S Yusuf S McQueen MJ Discordance analysis of apolipoprotein B and non-high density lipoprotein cholesterol as markers of cardiovascular risk in the INTERHEART study Atherosclerosis 2012 225 2 444 449 7. Mark L, Vallejo-Vaz AJ, Reiber I, Paragh G, Kondapally Seshasai SR, et al. Non-HDL cholesterol goal attainment and its relationship with triglyceride concentrations among diabetic subjects with cardiovascular disease: a nationwide survey of 2674 individuals in Hungary. Atherosclerosis. 2015;241(1):62-8. Mark L Vallejo-Vaz AJ Reiber I Paragh G Kondapally Seshasai SR et al Non-HDL cholesterol goal attainment and its relationship with triglyceride concentrations among diabetic subjects with cardiovascular disease: a nationwide survey of 2674 individuals in Hungary Atherosclerosis 2015 241 1 62 68 8. Kim SH, Baek SH. Lomitapide, relief pitcher for patients with homozygous familial hypercholesterolemia. Eur J Prev Cardiol.2019; 27(2) 155-6. Kim SH Baek SH Lomitapide, relief pitcher for patients with homozygous familial hypercholesterolemia Eur J Prev Cardiol 2019 27 2 155 156

Minieditorial referente ao artigo: Discordância entre Colesterol LDL e Não-HDL e Gravidade da Doença Arterial Coronária

 Short Editorial Discordance of Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol with Severity of Coronary Artery Disease 0000-0001-5123-3080 Castro Iran 1 Fontana Hugo Filho 1 Brazil Instituto de Cardiologia - Fundação Universitária de Cardiologia, Porto Alegre, RS - Brazil Mailing Address: Iran Castro • Instituto de Cardiologia - Métodos Gráficos - Av. Princesa Isabel, 395. Postal Code 90620-000, Santana, Porto Alegre, RS – Brazil E-mail: irancstro@gmail.com Cardiovascular Diseases/mortality Lipoproteins,LDL lipoproteins,HDL Coronary Artery Disease Hyydroxymethylglutaryl-CoA Reductase Inhibitors Proprotein Convertase 9

Cardiovascular diseases (CVDs) are the leading cause of mortality world.1 Dyslipidemia is a risk and causal factor and is the focus of the therapy for primary and secondary prevention of CVDs.

There is consensus and broad understanding of the causal mechanisms of low-density lipoproteins (LDL) in CVDs, and the benefit of the hypolipidemic therapy, with a magnitude of effect proportional to the reduction in serum levels.2 However, despite intensive use of lipid lowering agents, there remains a residual risk, a constant target of research and therapy.

Recent evidence confirms that the initial event of atherogenesis is the retention of LDL and other particles in the vessel wall.3 High non-HDL cholesterol levels help identify patients who despite having low serum LDL levels remain at high risk for cardiovascular events.4

The present study5 retrospectively evaluated the anatomical characteristics of 574 patients diagnosed with acute coronary syndrome and correlated the findings with LDL and non-HDL serum levels. There was 15% disagreement between LDL and non-HDL, which was similar to previous studies.6 However, no significant anatomical differences were identified in the assessment of the severity of atherosclerotic disease. Prior use of statins may have a more significant effect on LDL reduction than non-HDL, which may explain the lack of association.

In addition, the sensitivity of LDL levels in identifying cardiovascular risk is reduced in diabetes.7 In fact, the present study reported discrepancies in the association between diabetes mellitus and LDL levels. Perhaps the sample size was not adequate enough to evidence anatomical differences between the groups. The follow-up of patients with discrepant associations could identify a subgroup at higher risk of new events.

The Brazilian guideline already includes both LDL and non-HDL targets, seeking to identify individuals with high residual risk of cardiovascular events despite adequate LDL levels. Prospective studies will help better identify the subgroup of patients who require more intense treatment approach, who would probably benefit from more expensive and effective therapies such as PCSK9 inhibitor and Lomitapide.8 These drugs have already been shown to be effective in reducing cardiovascular events and apolipoprotein(a) in some groups of patients.

Short Editorial related to the article: Discordance of Low-Density Lipoprotein Cholestrol and Non-High-Density Lipoprotein Cholestrol and Coronary Artery Disease Severity