Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCF6pyPCMVQFMQ5tTC3psff8kS0066-782X201900010001810.5935/abc.20180264Short EditorialA New Marker of Myocardial Bridge?0000-0001-8121-5959VillelaPaolo Blanco120000-0002-0737-6188OliveiraGláucia Maria Moraes de12Universidade Federal do Rio de JaneiroRio de JaneiroRJBrazilUniversidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ - BrazilUniversidade Federal do Rio de JaneiroInstituto do Coração Edson SaadRio de JaneiroRJBrazilInstituto do Coração Edson Saad - UFRJ, Rio de Janeiro, RJ - BrazilMailing Address: Paolo Blanco Villela, Universidade Federal do Rio de Janeiro (UFRJ) - R. Prof. Rodolpho P. Rocco, 255 - 8º. andar - Sala 6. Postal Code 21941-913, Cidade Universitária, RJ - Brazil. E-mail: pbvillela@gmail.com1201911211819This 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 citedKeywordsMyocardial Bridging/physiopathologyInflammationAtherosclerosisRisk FactorsMonocytesLipoproteins, HDL
Myocardial bridges (MBs) have been associated with an increased incidence of cardiovascular events. Even though the pathophysiology of this association is still elusive, it seems to be related to the development of atherosclerosis. This hypothesis is based on changes in blood flow resulting from systolic compression of coronary arteries and leading to changes in arterial wall shear stress, which could act as a proatherogenic event affecting the endothelium of the arterial segment proximal to the MB.1
Recently, Akishima-Fukasawa et al.2 assessed 150 autopsies of individuals without cardiovascular heart disease to verify the influence of MBs on the development of atherosclerosis. The authors found the occurrence of MBs in 93 hearts, and using computer-assisted histomorphometry, observed a higher frequency of luminal stenosis in segments proximal to the MB. Using a multiple comparison test, the authors showed a relation between the presence of risk factors like hypertension, diabetes, and dyslipidemia to a higher rate of stenosis affecting segments located 2.5 cm proximally to the MB. Despite the absence of MB flow evaluation, the authors documented an anatomical association between significant atherosclerotic lesions and the presence of MBs.2 We could speculate that this may be one of the explanations for the increased incidence of cardiovascular events in patients with MB.
The detection of MBs by imaging methods has increased with the use of cardiac computed tomography, which allows for multiplanar and three-dimensional evaluations. Studies using this method have reported prevalence rates of MBs ranging from 5% to 76%, depending on the population studied and the type of MB and equipment used for its detection.3,4 However, the availability of this method for clinical use is limited.
In this issue of the Arquivos Brasileiros de Cardiologia, Enhos et al.5 proposed that a newly described tool for the assessment of inflammation and atherosclerosis - the relationship between monocytes and high-density lipoprotein (HDL), abbreviated as MHR (monocyte-to-HDL-cholesterol ratio) - could be associated with atherosclerosis in segments proximal to an MB. The authors studied 160 patients with MBs and without significant coronary lesions and observed that at a cut-off value of 13.55, the MHR was able to detect the presence of MBs with a 59% sensitivity, 65% specificity, and an area under the ROC curve of 0.687 (95% confidence interval 0.606-0.769, p < 0.001). On multivariate analysis, the MHR emerged as an independent risk factor for the presence of MB. The authors attributed this association to the occurrence of endothelial dysfunction and inflammation in patients with MB.5
Monocytes have a fundamental role in the inflammatory cascade and participate actively in the development and progression of the atherosclerotic plaque, while HDL particles behave otherwise, reducing the expression of tissue factor in monocytes, hindering cell migration and LDL oxidation in the vascular wall.6 Observations from biochemical assays have allowed a better understanding of the complex interactions between monocytes and HDL on atherogenesis, and both of them combined seem more appropriate to assess inflammation when compared with the measurement of each of them alone.6
The MHR has been associated with different clinical conditions with pathophysiological bases that include an inflammatory component. In regard to chronic coronary disease, Korkmaz et al.7 studied 301 patients with intermediate lesions undergoing functional evaluation by fractional flow reserve (FFR) and found that those with an FFR ≤ 0.8 showed the highest MHR values (11.6 ± 3.3 vs. 12.6 ± 2.5, respectively)7. In another study, Akboga et al.8 assessed the relationship between MHR and the SYNTAX score. In the study, which included 1229 patients, the highest MHR values were found in patients with a score equal to or greater than 23, demonstrating an association with the burden of atherosclerotic disease, according to the interpretation of the authors.8 The study by Enhos et al.5 excluded patients with known atherosclerotic disease, and since the authors found a positive association between MHR and MB, the inflammation present in both conditions seems to be the likely link.
In addition to being a marker associated with the presence of MB, the MHR has also demonstrated a possible association with prognosis in patients with this condition. In a study with 1598 patients with ST-elevation acute myocardial infarction, the group with the highest MHR tertile (30.1 ± 10.5) showed higher mortality and higher incidence of cardiovascular events during hospitalization and along a 5-year follow-up.9 The authors concluded that the MHR was an independent predictor of prognosis in these patients.9 Similar findings have been reported by Cetin et al.10 in a study with 2661 patients. The authors found an association between higher MHR and increased mortality, as well as an increased rate of stent thrombosis. The study by Enhos et al.5 does not allow conclusions about the prognosis of the patients.
In addition to coronary disease, studies have associated higher MHR values to diabetic nephropathy (in patients with diabetic nephropathy compared with healthy subjects and with patients with diabetes and without proteinuria),11 presence and severity of metabolic syndrome,12 presence of coronary ectasia,13 cardiac syndrome X,14 and smoking.15 Even though these results derived from observational studies, they suggest a relationship between conditions that cause vascular inflammation and MHR changes.
The study by Enhos et al.5 has several limitations, including a small cohort derived from a single center and an assessment of the MHR measured transversely, although no relevant differences were observed between individuals with MB and controls regarding factors that are known to influence the MHR. Additionally, other potential causes of alterations in this relationship were not evaluated, such as the practice of physical activity, diet, smoking, and the presence of other underlying inflammatory processes.
However, a great merit of the study is to present further evidence of a possible association between MBs and inflammation, which should be further evaluated in longitudinal studies verifying if the association relates to increased cardiovascular outcomes. Until such data become available, modification of diagnostic and therapeutic approaches based on the routine determination of this association in patients with MB does not seem relevant, considering that most MBs have a benign course and their treatment is still controversial.
References1 Corban MT, Hung OY, Eshtehardi P, Rasoul-Arzrumly E, McDaniel M, Mekonnen G, et al. Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies. J Am Coll Cardiol. 2014; 63(22):2346-55.CorbanMTHungOYEshtehardiPRasoul-ArzrumlyEMcDanielMMekonnenGMyocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategiesJ Am Coll Cardiol20146322234623552 Akishima-Fukasawa Y, Ishikawa Y, Mikami T, Akasaka Y, Ishii T. Settlement of stenotic site and enhancement of risk factor load for atherosclerosis in left anterior descending coronary artery by myocardial bridge. Arterioscler Thromb Vasc Biol. 2018; 38(6):1407-14.Akishima-FukasawaYIshikawaYMikamiTAkasakaYIshiiTSettlement of stenotic site and enhancement of risk factor load for atherosclerosis in left anterior descending coronary artery by myocardial bridgeArterioscler Thromb Vasc Biol2018386140714143 Lee MS, Chen CH. Myocardial bridging: an up todate review. J Invas Cardiol.2015;27(11):521-8.LeeMSChenCHMyocardial bridging: an up todate reviewJ Invas Cardiol201527115215284 Tarantini G, Migliore F, Cademartiri F, Fraccaro C, Iliceto S. Left Anterior Descending Artery Myocardial Bridging: A Clinical Approach. J Am Coll Cardiol. 2016; 68(25):2887-99.TarantiniGMiglioreFCademartiriFFraccaroCIlicetoSLeft Anterior Descending Artery Myocardial Bridging: A Clinical ApproachJ Am Coll Cardiol20166825288728995 Enhos A, Cosansu K, Huyut MA, Turna F, Karacop E, Bakshaliyev N et al. Assessment of the relationship between monocyte to high-density lipoprotein ratio and myocardial bridge. Arq Bras Cardiol. 2019; 112(1):12-17EnhosACosansuKHuyutMATurnaFKaracopEBakshaliyevNAssessment of the relationship between monocyte to high-density lipoprotein ratio and myocardial bridgeArq Bras Cardiol2019112112176 Ganjali S, Gotto AM Jr, Ruscica M, Atkin SL, Butler AE, Banach M, et al. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol. 2018; 233(12):9237-46.GanjaliSGottoAMJrRuscicaMAtkinSLButlerAEBanachMMonocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseasesJ Cell Physiol201823312923792467 Korkmaz A, Demir M, Unal S, Yildiz A, Ozyazgan B, Demirtas B, et al. Monocyte-to-high density lipoprotein ratio (MHR) can predict the significance of angiographically intermediate coronary lesions. Int J Cardiovasc Acad. 2017;3(1-2):16-20.KorkmazADemirMUnalSYildizAOzyazganBDemirtasBMonocyte-to-high density lipoprotein ratio (MHR) can predict the significance of angiographically intermediate coronary lesionsInt J Cardiovasc Acad201731-216208 Akboga MK, Balci KG, Maden O, Ertem AG, Kirbas O, Yayla C, et al. Usefulness of monocyte to HDL-cholesterol ratio to predict high SYNTAX score in patients with stable coronary artery disease. Biomark Med. 2016; 10(4):375-83.AkbogaMKBalciKGMadenOErtemAGKirbasOYaylaCUsefulness of monocyte to HDL-cholesterol ratio to predict high SYNTAX score in patients with stable coronary artery diseaseBiomark Med20161043753839 Açikgöz SK, Açikgöz E, Sensoy B, Topal S, Aydogdu S. Monocyte to high-density lipoprotein cholesterol ratio is predictive of in-hospital and five-year mortality in ST-segment elevation myocardial infarction. Cardiol J. 2016;23(5):505-12.AçikgözSKAçikgözESensoyBTopalSAydogduSMonocyte to high-density lipoprotein cholesterol ratio is predictive of in-hospital and five-year mortality in ST-segment elevation myocardial infarctionCardiol J201623550551210 Cetin MS, Ozcan Cetin EH, Kalender E, Aydin S, Topaloglu S, et al. Monocyte to HDL cholesterol ratio predicts coronary artery disease severity and future major cardiovascular adverse events in acute coronary syndrome. Heart Lung Circ. 2016; 25(11):1077-86.CetinMSOzcan CetinEHKalenderEAydinSTopalogluSMonocyte to HDL cholesterol ratio predicts coronary artery disease severity and future major cardiovascular adverse events in acute coronary syndromeHeart Lung Circ201625111077108611 Karatas A, Turkmen E, Erdem E, Dugeroglu H, Kaya Y. Monocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathy. Biomark Med. 2018; 12(9):953-9.KaratasATurkmenEErdemEDugerogluHKayaYMonocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathyBiomark Med201812995395912 Uslu AU, Sekin Y, Tarhan G, Canakci N, Gunduz M, Karagulle M. Evaluation of monocyte to high-density lipoprotein cholesterol ratio in the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost. 2018; 24(5):828-33.UsluAUSekinYTarhanGCanakciNGunduzMKaragulleMEvaluation of monocyte to high-density lipoprotein cholesterol ratio in the presence and severity of metabolic syndromeClin Appl Thromb Hemost201824582883313 Kundi H, Gok M, Kiziltunc E, Cetin M, Cicekcioglu H, Cetin ZG, et al. Relation between monocyte to high-density lipoprotein cholesterol ratio with presence and severity of isolated coronary artery ectasia. Am J Cardiol. 2015; 116(11):1685-9.KundiHGokMKiziltuncECetinMCicekciogluHCetinZGRelation between monocyte to high-density lipoprotein cholesterol ratio with presence and severity of isolated coronary artery ectasiaAm J Cardiol2015116111685168914 Dogan A, Oylumlu M. Increased monocyte-to-HDL cholesterol ratio is related to cardiac syndrome X. Acta Cardiol. 2017; 72(5):516-21.DoganAOylumluMIncreased monocyte-to-HDL cholesterol ratio is related to cardiac syndrome XActa Cardiol2017725516521MinieditorialNovo Marcador para a Presença de Ponte Miocárdica?0000-0001-8121-5959VillelaPaolo Blanco120000-0002-0737-6188OliveiraGláucia Maria Moraes de12Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ - BrasilInstituto do Coração Edson Saad - UFRJ, Rio de Janeiro, RJ - BrasilCorrespondência: Paolo Blanco Villela, Universidade Federal do Rio de Janeiro (UFRJ) - R. Prof. Rodolpho P. Rocco, 255 - 8º. andar - Sala 6. CEP 21941-913, Cidade Universitária, RJ - Brasil. E-mail: pbvillela@gmail.comPalavras-chavePonte Miocárdica/fisiopatologiaInflamaçãoAteroscleroseFatores de RiscoMonócitosLipoproteínas de Alta Densidade (HDL)
As pontes miocárdicas (PM) têm sido associadas à incidência aumentada de eventos cardiovasculares, porém apresentam fisiopatologia ainda não esclarecida, parecendo estar relacionadas com o desenvolvimento de aterosclerose. As razões apontadas são as alterações do fluxo sanguíneo decorrentes da compressão sistólica da artéria coronária acometida que acarretaria alteração na tensão de cisalhamento da parede do vaso, e que poderia agir como fator pró-aterogênico afetando o endotélio do segmento do vaso proximal à PM.1
Recentemente, Akishima-Fukasawa et al.2 avaliaram 150 autopsias de indivíduos sem doença cardiovascular com o objetivo de verificar a influência das PM sobre o desenvolvimento de aterosclerose, identificando a presença de PM em 93 deles. Empregando a histofotometria assistida por computador, os autores observaram maior frequência de estenose luminal nos segmentos proximais relacionados às PM. Utilizando teste de comparação múltipla, relacionaram a presença de fatores de risco como hipertensão, diabetes e dislipidemia, com maior taxa de estenose que ocorreu nos 2,5 cm proximais à PM. Apesar da ausência de avaliação de fluxo, os autores documentaram a associação anatômica entre as lesões ateroscleróticas significativas e as PM.2 Podemos especular que essa poderia ser uma das explicações para a incidência aumentada de eventos cardiovasculares em pacientes com PM.
A detecção das PM através de métodos de imagem aumentou com o emprego a tomografia cardíaca computadorizada, que permite avaliações multiplano e tridimensional. Estudos com esse método reportaram uma prevalência que variou de 5% a 76% na dependência da população estudada, do tipo de aparelho empregado e do padrão da PM.3,4 No entanto, a disponibilidade desse método para uso clínico é limitada.
Nesta edição da revista Arquivos Brasileiros de Cardiologia, Enhos et al.,5 propuseram que uma nova ferramenta para avaliação de inflamação e aterosclerose, a relação entre os monócitos e a lipoproteína de alta densidade - HDL (RMH), poderia estar associada com a aterosclerose nos segmentos proximais das PM. Os autores estudaram 160 pacientes com PM e ausência de lesões coronarianas significativas, e observaram que um ponto de corte de 13,55 para a RMH apresentou sensibilidade de 59%, especificidade de 65% e área sob a curva ROC de 0,687 (IC 95: 0,606-0,769, p < 0,001), sendo um fator independente para a presença das PM na análise multivariada. Os autores atribuíram esses achados à disfunção endotelial e à inflamação.5
Os monócitos apresentam papel fundamental na cascata inflamatória e participam ativamente dos processos de formação e progressão da placa aterosclerótica, enquanto as partículas de HDL atuam de maneira contrária, reduzindo a expressão de fator tecidual nos monócitos, dificultando a migração celular e a oxidação do LDL na parede vascular.6 Observações realizadas a partir de ensaios bioquímicos permitiram compreender melhor as interações complexas entre monócitos e HDL na aterogênse, e a relação parece ser mais adequada para avaliar inflamação quando comparada às dosagens isoladas de seus componentes.6
A RMH foi associada a diversas condições clínicas nas quais a base fisiopatológica inclui o componente inflamatório. Em pacientes com doença coronariana crônica, Korkmaz et al.,7 estudaram 301 pacientes com lesões intermediárias que foram submetidos à avaliação funcional por Reserva de Fluxo Fracionada (FFR) e os pacientes que apresentaram FFR ≤ 0,8 apresentaram também os maiores valores da RMH (11,6 ± 3,3 vs. 12,6 ± 2,5).7 Em outro estudo, Akboga et al.8 avaliaram a relação entre RMH e o escore SYNTHAX. Neste estudo com 1229 pacientes, os maiores valores da RMH foram encontrados naqueles que apresentaram escore igual ou superior a 23, demonstrando associação com carga de doença aterosclerótica, segundo interpretação dos autores.8 No estudo de Enhos et al.5 os pacientes com doença aterosclerótica conhecida foram excluídos, e como foi encontrada associação positiva entre RHM e PM, o provável elo se dá pela inflamação presente em ambas as condições.
Além de marcador associado ao diagnóstico, a RMH também demonstrou possível associação com prognóstico. Em estudo com 1598 pacientes que apresentaram infarto agudo do miocárdio com supradesnível do segmento ST, o grupo de maior tercil da RHM (30,1 ± 10,5) apresentou maior mortalidade e também maior incidência de eventos cardiovasculares maiores tanto na fase intra-hospitalar, quanto ao longo do seguimento de 5 anos.9 Os autores concluíram que a RMH foi preditor independente de prognóstico nesses pacientes.9 Achados semelhantes foram encontrados por Cetin et al.10 em estudo com 2661 pacientes, no qual além da maior RMH ter sido associada com maior mortalidade, foi observado também aumento da taxa de trombose de stent. O estudo de Enhos et al.5 não permite conclusões a respeito do prognóstico.
Além da doença coronariana, estudos associaram maiores valores da RMH à nefropatia diabética quando comparados a indivíduos saudáveis e a diabéticos sem proteinúria;11 à presença e gravidade da síndrome metabólica;12 à presença de ectasias coronarianas;13 à síndrome X,14 e ao tabagismo.15 Estes dados, embora oriundos de estudos observacionais, sugerem relação entre condições que provocam inflamação vascular e alterações na RMH.
O estudo de Enhos et al.,5 apresenta várias limitações, como casuística reduzida proveniente de um único centro, com avaliação da RMH aferida de forma transversal, embora não houvesse diferenças relevantes entre os portadores de PM e os controles quanto aos fatores que sabidamente influenciam a RMH. Por outro lado, não foram avaliadas outras potenciais causas de alteração dessa relação como realização de atividade física, dieta, tabagismo e a presença de outros processos inflamatórios subjacentes.
Entretanto, o grande valor deste estudo consiste em apresentar evidência de possível associação entre PM e inflamação que precisará ser avaliada de forma longitudinal para verificar sua associação com o aparecimento de desfechos cardiovasculares aumentados em pacientes com PM. Até que esses dados sejam obtidos, não nos parece relevante a realização da aferição dessa relação em pacientes que apresentem PM com objetivo de modificação de abordagem diagnóstica e terapêutica, uma vez que se trata de uma condição benigna na maioria dos casos, com tratamento ainda controverso.