abcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCSão Paulo, SP, BrazilC8PpXWPttx5sN4m6fzcbGdwS0066-782X2013000500005S0066-782X(13)1000050000510.5935/abc.20130057Artigos OriginaisRelação entre índice tornozelo-braquial e doença aterosclerótica carotídeaBrasileiroAugusto Cezar LacerdaOliveiraDinaldo Cavalcanti deVictorEdgar GuimarãesOliveiraDanielle A. G. CavalcantiBatistaLaecio LeitãoRecifePernambucoUniversidade Federal de PernambucoHospital das Clínicas Brazil0520131005422428070620121401201208122012This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
FUNDAMENTO: A associação do índice tornozelo-braquial (ITB) com a medida do complexo médio intimal das artérias carótidas (MCMI) não está amplamente estudada. OBJETIVO: Objetivamos avaliar se pacientes com ITB < 0,9 apresentam maior prevalência de placa aterosclerótica carotídea do que aqueles com ITB > 0,9. MÉTODOS: No período de janeiro a dezembro de 2011, recrutamos 118 pacientes (48 homens e 70 mulheres) que tiveram seus ITB e MCMI mensurados. Os pacientes foram divididos em grupo 1 (ITB < 0,9) e grupo 2 (ITB > 0,9). Utilizamos os testes de Mann-Whitney, qui-quadrado e Fischer para comparações entre os grupos. Para avaliar correlação entre ITB e MCMI empregamos a correlação de Pearson. RESULTADOS: A prevalência de ITB < 0,9 foi 29,7%, enquanto a da MCMI > 1,5 mm de 34,7%. Não houve diferença de características clínicas entre os grupos 1 e 2: idade média (64 ± 9 vs. 62 ± 7,2 anos, p = 0,1), homens (40% vs. 41%, p = 0,9), hipertensão (74% vs. 59%, p = 0,1), diabetes melito (54% vs. 35%, p = 0,051), dislipidemia 26% vs. 24%, p = 0,8), tabagismo (57% vs. 65%, p = 0,4). A prevalência de placa carotídea foi maior no grupo 1 (48,6% vs. 28,9%, p = 0,04). A correlação de Pearson entre o ITB e a MCMI foi de - 0,235, com valor de p = 0,01. CONCLUSÕES: Pacientes com ITB < 0,9 apresentaram maior prevalência de aterosclerose carotídea. Houve correlação negativa entre o ITB e a MCMI.
Índice Tornozelo-BraçoDoenças das Artérias CarótidasUltrassonografia09042013
Relação entre índice tornozelo-braquial e doença aterosclerótica carotídea
Augusto Cezar Lacerda Brasileiro; Dinaldo Cavalcanti de Oliveira; Edgar Guimarães Victor; Danielle A. G. Cavalcanti Oliveira; Laecio Leitão Batista
Hospital das Clínicas da UFPE, Recife, PE - Brasil
Correspondência
RESUMO
FUNDAMENTO: A associação do índice tornozelo-braquial (ITB) com a medida do complexo médio intimal das artérias carótidas (MCMI) não está amplamente estudada.
OBJETIVO: Objetivamos avaliar se pacientes com ITB < 0,9 apresentam maior prevalência de placa aterosclerótica carotídea do que aqueles com ITB > 0,9.
MÉTODOS: No período de janeiro a dezembro de 2011, recrutamos 118 pacientes (48 homens e 70 mulheres) que tiveram seus ITB e MCMI mensurados. Os pacientes foram divididos em grupo 1 (ITB < 0,9) e grupo 2 (ITB > 0,9). Utilizamos os testes de Mann-Whitney, qui-quadrado e Fischer para comparações entre os grupos. Para avaliar correlação entre ITB e MCMI empregamos a correlação de Pearson.
RESULTADOS: A prevalência de ITB < 0,9 foi 29,7%, enquanto a da MCMI > 1,5 mm de 34,7%. Não houve diferença de características clínicas entre os grupos 1 e 2: idade média (64 ± 9 vs. 62 ± 7,2 anos, p = 0,1), homens (40% vs. 41%, p = 0,9), hipertensão (74% vs. 59%, p = 0,1), diabetes melito (54% vs. 35%, p = 0,051), dislipidemia 26% vs. 24%, p = 0,8), tabagismo (57% vs. 65%, p = 0,4). A prevalência de placa carotídea foi maior no grupo 1 (48,6% vs. 28,9%, p = 0,04). A correlação de Pearson entre o ITB e a MCMI foi de - 0,235, com valor de p = 0,01.
CONCLUSÕES: Pacientes com ITB < 0,9 apresentaram maior prevalência de aterosclerose carotídea. Houve correlação negativa entre o ITB e a MCMI.
Palavras-chave: Índice Tornozelo-Braço, Doenças das Artérias Carótidas, Ultrassonografia / métodos.
Introdução
A aterosclerose é uma doença que atinge o sistema arterial de forma crônica e sistêmica, decorrente de uma resposta inflamatória juntamente com reações imunes1. Acontece desde as fases iniciais da vida, resultando da predisposição genética e exposição a fatores de risco que provocam disfunção endotelial2,3.
A doença arterial periférica (DAP) refere-se às alterações causadas pela aterosclerose na parede da aorta e dos seus ramos, com exceção das coronárias. O conceito atual de DAP é estabelecido por exames não invasivos, como o índice tornozelo-braquial (ITB) e a medida do complexo médio-intimal (MCMI), antes mesmo do surgimento de qualquer sintoma clínico4.
O ITB anormal indica comprometimento obstrutivo das artérias dos membros inferiores e está associado a risco de eventos cardiovasculares (ECV), particularmente infarto agudo do miocárdio (IAM) e acidente vascular encefálico (AVE), independente de outros fatores de risco5-7.
O espessamento da parede carotídea, diagnosticado pela ultrassonografia no modo B, representa uma alteração vascular subclínica, que pode progredir para doença aterosclerótica. O valor numérico da MCMI das artérias carótidas é utilizado para estratificação do risco de ECV8,9.
A medida do ITB e a do complexo médio-intimal (CMI) são de baixo custo, reprodutíveis e sem riscos associados. Ambas são consideradas de referência para o diagnóstico da doença aterosclerótica. O ITB avalia o acometimento nos membros inferiores, enquanto a MCMI, a doença nas artérias carótidas. A associação entre tais medidas é descrita, sugerindo uma relação inversa, além disso funcionam como marcadores independentes para ECV10,11.
O objetivo primário deste estudo foi avaliar se pacientes com ITB < 0,9 apresentariam maior prevalência de aterosclerose carotídea quando comparados àqueles com índice > 0,9. Os objetivos secundários foram analisar a associação entre ITB e o espessamento do CMI, assim como verificar a existência de possível correlação entre os valores numéricos do ITB e da MCMI.
Métodos
O estudo seguiu os princípios éticos da Declaração de Helsinque (WMA, 2000) e da resolução 196/96 do Conselho Nacional de Saúde (CNS, 1996), sendo aprovado pelo Comitê de Ética em Pesquisa envolvendo seres humanos da instituição, em 20 de abril de 2011 conforme protocolo nº 426/2010.
Desenho do estudo
Estudo prospectivo, transversal, analítico, com período de recrutamento definido entre maio e dezembro de 2011.
Critérios de inclusão
Foram incluídos pacientes com idade entre 50 e 69 anos que fossem diabéticos e/ou tabagistas, ou que tivessem idade acima de 70 anos independente de fatores de risco. Também foi exigida assinatura do termo de consentimento livre e esclarecido do estudo.
Critérios de exclusão
Foram considerados critérios de exclusão: câncer avançado, revascularização percutânea ou cirúrgica das artérias dos membros inferiores ou das artérias carótidas, doença hepática terminal, impossibilidade técnica de medição do índice tornozelo-braquial ou do complexo médio-intimal carotídeo, pacientes submetidos à amputação de membros e ITB > 1,4.
População do estudo
Entre abril e dezembro de 2011, recrutamos 118 pacientes, atendidos no ambulatório especializado de cirurgia cardiovascular de um hospital terciário, que preencheram os critérios de inclusão e não apresentaram nenhum dos critérios de exclusão do estudo.
Análise estatística
Para comparação dos grupos (ITB > 0,9 vs. ITB < 0,9) com relação às variáveis qualitativas, foi aplicado o teste qui-quadrado de Pearson ou exato de Fisher, quando necessário. Para a comparação das variáveis quantitativas da MCMI na carótida comum (MCMI-CC), na carótida interna (MCMI-CINT), na carótida externa (MCMI-CEX) e geral (MCMI-GERAL), que foi o máximo entre todos os valores, foi aplicado o teste não paramétrico de Mann-Whitney, devido a não normalidade dessas variáveis. No caso da comparação dos valores de ITB na forma quantitativa com as medidas do complexo médio-intimal na carótida, foi realizada uma análise de correlação através do coeficiente de correlação de Pearson.
Os cálculos estatísticos foram executados no software SPSS for Windows versão 18.0 - Statistical Package for the Social Sciences.
Protocolo do índice tornozelo-braquial
Para aferição do ITB utilizou-se um sonar Doppler modelo DV 610 da empresa Medmega e um aparelho esfignomanômetro com braçadeira de 12 cm de largura e comprimento variando de 29 a 40 cm.
Todas as medidas foram feitas com o paciente em decúbito dorsal após 10 minutos de repouso, sendo medida a pressão sistólica da artéria tibial posterior, da artéria dorsal do pé e da artéria braquial bilateralmente. Dividiu-se a maior das pressões no tornozelo pela maior pressão sistólica encontrada na artéria braquial dos membros superiores, obtendo-se assim o ITB12,13.
Os valores considerados normais para o ITB estão entre 0,9 e 1,4. Assim, índices maiores que 1,4 representam incompressão das artérias e índices menores ou iguais a 0,9 demonstram a presença de doença arterial periférica (DAP)12.
Protocolo da medida do complexo médio-intimal carotídeo
A medida do complexo médio-intimal foi realizada com equipamento de ultrassonografia modelo X8 da Medison com transdutor linear 7,5-12 MHz. A artéria carótida comum foi avaliada, bilateralmente, utilizando software automático (auto-IMTTM) e as artérias carótidas interna e externa foram estudadas, também, bilateralmente, através de medidas manuais.
A profundidade do campo foi de 30-40 mm. Houve ajuste de ganho com pouco artefato intraluminal, não se utilizou harmônica e houve monitorização do ciclo cardíaco através do ECG acoplado na imagem para verificação no final da diástole14-16.
Observou-se na parede posterior das artérias, uma linha dupla que representa as três camadas da parede arterial. A primeira linha é a interface entre o sangue e a camada íntima (lúmen anecoico e a íntima ecogênica), enquanto a segunda linha, a interface entre a camada média e a adventícia (média hipoecoica e a adventícia ecogênica)17.
Espessamento da MCMI acontece entre > 0,9 mm e < 1,5 mm, porém quando a medida for > 1,5 mm, considera-se placa aterosclerótica18.
Fluxograma do estudo
Os pacientes foram divididos em 2 grupos, sendo o grupo 1 constituído pelos que tinham ITB < 0,9 e grupo 2 pelos com este índice > 0,9. As variáveis clínicas, as MCMI e a prevalência de placa carotídea foram comparadas entre os grupos. Foi testada a possibilidade de existência de correlação linear entre os valores numéricos da MCMI e do ITB.
Para fins da análise, consideramos as MCMI das artérias carótidas comum, interna e externa. De cada território foi coletada as medidas da direita e esquerda, mas na análise estatística considerou-se a maior delas. Definimos máxima MCMI como o maior valor encontrado, independentemente da artéria carótida avaliada.
Resultados
No período do estudo, 362 pacientes foram atendidos no ambulatório de cirurgia vascular. Destes, 118 (32,5%) pacientes preencheram os critérios de inclusão e não apresentaram nenhum dos critérios de exclusão do estudo, sendo recrutados.
A prevalência de ITB < 0,9 foi de 29,7% (35 pacientes), enquanto a de ITB > 0,9 de 70,3% (83 pacientes). A MCMI > 0,9 ocorreu em 69,5% dos pacientes e a placa aterosclerótica carotídea em 34,7%.
A Tabela 1 revela que não houve diferença do perfil clínico entre os grupos. Entretanto, a prevalência de ITB < 0,9 foi maior em pacientes com idade > 70 anos (Tabela 2).
A comparação entre os grupos revelou que no grupo 1 (ITB < 0,9) houve maior MCMI na carótida interna [ 1,4 mm (max: 0,6 mm - min: 3,5 mm ) vs. 1 mm (max: 0,5 mm - min: 3,8mm), p = 0,04] e carótida externa [0,7 mm (max: 0,5 mm - min: 3,2 mm) vs. 0,6 mm (max: 0,4 mm - min: 2,3mm), p = 0,047]. A máxima MCMI foi maior nos pacientes com ITB < 0,9 [1,4 mm (max: 0,7 mm - min: 3,5 mm) vs. 1 mm (max: 0,6 mm - min: 3,8 mm), p = 0,01) (Tabela 3).
A prevalência de placa aterosclerótica foi 48,6% (17 pacientes) nos pacientes com ITB < 0,9 e de 28,9% (24 pacientes) naqueles com este índice > 0,9 ( p = 0,04).
A correlação de Pearson entre o ITB e a máxima MCMI foi de - 0,234, sendo o valor de p = 0,01 (Gráfico 1).
Discussão
Nosso estudo revelou que pacientes com ITB < 0,9 apresentaram maior MCMI das artérias carótidas interna e externa, assim como máximo valor da MCMI no território carotídeo. Destaque-se ainda que a prevalência de aterosclerose carotídea foi maior nos pacientes com ITB anormal.
O ITB é produto da redução quantitativa da pressão arterial sistólica nos membros inferiores provocada por obstrução aterosclerótica proximal5. Em um primeiro momento, imagina-se que isso ocorra em fases avançadas da aterosclerose. Entretanto, embora a doença aterosclerótica seja sistêmica, existem fatores locais vasculares que talvez possam influenciar no acúmulo do ateroma e obstrução do vaso19.
Por outro lado, o espessamento do complexo médio-intimal é considerado marca de aterosclerose precoce e preditor de risco de doença cardiovascular20-22.
Estudos de avaliação temporal seriada dos valores de ITB e CMI poderiam explicar vários aspectos desses testes, assim como da doença aterosclerótica em territórios vasculares periféricos.
Pesquisadores têm estudado o ITB e a MCMI e neste contexto Allan e cols.23 avaliaram 1106 pacientes, com idade entre 55 e 74 anos, incluídos no Edinburgh Artery Study e procuraram associações entre ITB e MCMI. Observaram que a MCMI foi maior nos homens e que pacientes mais velhos apresentaram maior valor do complexo médio-intimal. Houve correlação linear negativa entre ITB e MCMI (r = - 0,116, p = 0,06).
Pacientes com ITB < 0,9 tiveram maior MCMI do que aqueles com ITB > 0,9 [0,87 mm (0,83 mm - 0,91 mm) vs. 0,8 mm (0,79 mm - 0,82 mm) p = 0,01]. No subgrupo de pacientes com claudicação, os valores numéricos da MCMI foram os maiores [(0,90 mm (0,85 mm - 0,95 mm)]23.
Dois outros estudos também demonstraram que pacientes com ITB < 0,9 apresentam maior MCMI quando comparados àqueles com este índice > 0,924,25.
Nossos achados de maior MCMI em pacientes com ITB < 0,9 são concordantes com os estudos descritos anteriormente. Entretanto, nossos valores da MCMI foram maiores do que os dos estudos citados e acreditamos que esse fato seja justificado porque recrutamos pacientes com perfil clínico de maior risco para doença aterosclerótica periférica avançada.
Saliente-se que, de acordo com a literatura, pacientes com PAD mais avançada, ou seja, com claudicação, tiveram maiores valores da MCMI do que a população geral26.
Acreditamos que pacientes com obstruções significativas das artérias dos membros inferiores apresentam aterosclerose em fase mais avançada e por isso tenham maior possibilidade de terem maior MCMI e maior prevalência de placa carotídea.
Há duas décadas, o estudo de Rotterdam10, que incluiu pacientes da população geral com idade > 55 anos, revelou que a prevalência de ITB < 0,9 foi 11,9%, que o aumento de 0,1 mm na MCMI esteve associado à redução de 0,026 do ITB e que pacientes com claudicação apresentavam menores valores de ITB e maiores valores de MCMI quando comparados à população sem tal sintoma.
Nossa pesquisa, na qual a prevalência de ITB anormal foi 29,7%, demonstrou haver uma correlação linear negativa entre a MCMI e o valor numérico do ITB. Este achado reforça a hipótese sugerida há mais de 20 anos pelos pesquisadores do estudo de Rotterdam.
O estudo de Parv e cols.27 já havia encontrado uma correlação linear negativa entre o ITB e a MCMI (r = - 0,157). No entanto, nosso valor numérico do "r" da correlação foi maior e acreditamos que a gravidade da doença arterial periférica do nosso grupo pode ser um dos fatores para justificar tal achado.
Fundamentados no conceito que o ITB diminui com a progressão das obstruções proximais dos membros inferiores e a MCMI aumenta com o progredir da aterosclerose carotídea, seria esperado encontrar uma correlação linear negativa entre essas duas medidas. Tal correlação foi encontrada em nosso estudo.
A literatura mostra apenas uma sugestão de correlação linear negativa entre ITB e MCMI23, sendo possível, portanto, que esta esteja presente em apenas determinados subgrupos de pacientes e/ou fases da aterosclerose. Assim, inferimos que em pacientes com aterosclerose mais avançada tal correlação pode estar presente.
Quando o valor da MCMI é > 1,5 mm, afirma-se que existe placa aterosclerótica nas artérias carótidas18. Tal achado está associado à maior chance de infarto do miocárdio e acidente vascular encefálico para os pacientes28.
Pacientes com ITB < 0,9, no nosso estudo, apresentaram maior prevalência (próximo a 50%) de placa aterosclerótica quando comparados àqueles com este índice normal.
As principais limitações do nosso estudo são: necessidade de escolha de um valor normal de MCMI, pois não existe consenso na literatura, ausência de controles provenientes da população geral, o que permitiria avaliar diferentes fases de aterosclerose, não avaliação temporal seriada do ITB e MCMI, não possibilidade de cálculo amostral probabilístico, pois não existe consenso da prevalência de placa aterosclerótica carotídea diagnosticada por ultrassom Doppler em pacientes diabéticos e/ou tabagistas com ITB < 0,9. Saliente-se que é possível, a partir das taxas de prevalência de aterosclerose carotídea encontradas no nosso estudo, o desenvolvimento de estudos semelhantes com cálculo amostral.
Conclusões
Nosso estudo revelou que a prevalência de DAP, na população estudada, é alta, estando de acordo com a literatura. Além disso, o ITB < 0,9 está relacionado à maior prevalência de espessamento e de placa aterosclerótica nas carótidas e que a relação entre esses dois exames é inversa.
Dinaldo Cavalcanti de Oliveira
Rua Padre Landim, 302, apto 403, Madalena
CEP 50710-470, Recife, PE - Brasil
E-mail:
dinaldo@cardiol.br,
dinaldoc@ig.com.br
Artigo recebido em 07/06/12, revisado em 08/12/12, aceito em 14/01/13.
ERRATA
A versão de Relação entre Índice Tornozelo-Braquial e Doença Aterosclerótica Carotídea, publicada pelos Arquivos Brasileiros de Cardiologia em ahead of print, sofreu a seguinte alteração por solicitação do autor: substituir o nome José Laercio Leitão por Laecio Leitão Batista.
1. Lane HA, Smith JC, Davies JS. Noninvasive assessment of preclinical atherosclerosis. Vasc Health Risk Manag. 2006;2(1):19-30.Noninvasive assessment of preclinical atherosclerosisVasc Health Risk Manag2006193012LaneHASmithJCDaviesJS2. Hixson JE. Apolipoprotein E polymorphisms affect atherosclerosis in young males: Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1991;11(5):1237-44.Apolipoprotein E polymorphisms affect atherosclerosis in young males: Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research GroupArterioscler Thromb1991123744511HixsonJE3. Najjar SS, Scuteri A, Lakatta EG. Arterial aging: is it an immutable cardiovascular risk factor ?. Hypertension. 2005;46(3):454-62.Arterial aging: is it an immutable cardiovascular risk factor?Hypertension200545462346NajjarSSScuteriALakattaEG4. Hirsh AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol. 2006;47(6):1239-312.ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease FoundationJ Am Coll Cardiol20061239312647HirshATHaskalZJHertzerNRBakalCWCreagerMAHalperinJL5. Hooi JD, Kester AD, Stoffers HE, Rinkens PE, Knottnerus JA, van Ree JW. Asymptomatic peripheral arterial occlusive disease predicted cardiovascular morbity and mortality in a 7 year follow-up study. J Clin Epidemiol. 2004;57(3):294-300.Asymptomatic peripheral arterial occlusive disease predicted cardiovascular morbity and mortality in a 7 year follow-up studyJ Clin Epidemiol2004294300357HooiJDKesterADStoffersHERinkensPEKnottnerusJAvan ReeJW6. Markdisse M, Pereira Ada C, Brasil Dde P, Borges JL, Machado-Coelho GL, Krieger JE, et al. Prevalence and risk factors associated with peripheral arterial disease in the hearts of Brazil project. Arq Bras Cardiol. 2008;91(6):370-82.Prevalence and risk factors associated with peripheral arterial disease in the hearts of Brazil projectArq Bras Cardiol200837082691MarkdisseMPereira AdaCBrasil DdePBorgesJLMachado-CoelhoGLKriegerJE7. Newman AB, Siscovick DS, Manolio TA, Polak J, Fried LP, Borhani NO, et al. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative Reserch Group. Circulation. 1993;88(3):837-45.Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study: Cardiovascular Health Study (CHS) Collaborative Reserch GroupCirculation199383745388NewmanABSiscovickDSManolioTAPolakJFriedLPBorhaniNO8. Poredos P. Intima-media thichness: indicator of cardiovascular risk and measure of the extent of atherosclerosis. Vasc Med. 2004;9(1):46-54.Intima-media thichness: indicator of cardiovascular risk and measure of the extent of atherosclerosisVasc Med2004465419PoredosP9. Labropoulos N, Ashraf-Mansour M, Kang SS, Oh DS, Buckman J, Baker WH. Viscoelastic properties of normal and atherosclerotic carotid arteries. Eur J Vasc Endovasc Surg. 2000;19(3):221-5.Viscoelastic properties of normal and atherosclerotic carotid arteriesEur J Vasc Endovasc Surg20002215319LabropoulosNAshraf-MansourMKangSSOhDSBuckmanJBakerWH10. Bots ML, Hofman A, Grobbee DE. Common carotid intima-media thickness and lower extremity arterial atherosclerosis: the Rotterdam Study. Arterioscler Thromb. 1994;14(12):1885-91.Common carotid intima-media thickness and lower extremity arterial atherosclerosis: the Rotterdam StudyArterioscler Thromb19941885911214BotsMLHofmanAGrobbeeDE11. Price JF, Tzoulaki I, Lee AJ, Fowkes GR. Ankle brachial index and intima media thickness predict cardiovascular events similarly and inceased prediction when combined. J Clin Epidemiol. 2007;60(10):1067-75.Ankle brachial index and intima media thickness predict cardiovascular events similarly and inceased prediction when combinedJ Clin Epidemiol20071067751060PriceJFTzoulakiILeeAJFowkesGR12. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5-67.Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)J Vasc Surg2007S56745NorgrenLHiattWRDormandyJANehlerMRHarrisKAFowkesFG13. Carter SA: Indirect systolic pressure and pulse waves in arterial occlusive disease of the lower extremities. Circulation. 1968;37(4):624-37.Indirect systolic pressure and pulse waves in arterial occlusive disease of the lower extremitiesCirculation196862437437CarterSA14. Coll B, Feinstein SB. Carotid intima-media thickness measurements: techniques and clinical relevance. Curr Atheroscler Rep. 2008;10(5):444-50.Carotid intima-media thickness measurements: techniques and clinical relevanceCurr Atheroscler Rep200844450510CollBFeinsteinSB15. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis. 2007;23(1):75-80.Mannheim carotid intima-media thickness consensus (2004-2006): An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006Cerebrovasc Dis20077580123TouboulPJHennericiMGMeairsSAdamsHAmarencoPBornsteinN16. Roman MJ, Naqvi TZ, Gardin JM, Gerhard-Herman M, Jaff M, Mohler E. Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society of Vascular Medicine and Biology. J Am Soc Echocardiogr. 2006;19(8):943-54.Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society of Vascular Medicine and BiologyJ Am Soc Echocardiogr200694354819RomanMJNaqviTZGardinJMGerhard-HermanMJaffMMohlerE17. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation. 1986;74(6):1399-406.Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imagingCirculation19861399406674PignoliPTremoliEPoliAOrestePPaolettiR18. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Desvarieux M, et al. Mannhein intima-media thickness consensus. Cerebrovasc Dis. 2004;18(4):346-9.Mannhein intima-media thickness consensusCerebrovasc Dis20043469418TouboulPJHennericiMGMeairsSAdamsHAmarencoPDesvarieuxM19. Zarins CK, Xu C, Glagov S. Patologia da parede arterial na aterosclerose. In: Rutherford RB. (editor). Cirurgia vascular. Rio de Janeiro: Dilivros; 2007. p. 123.Cirurgia vascular2007123ZarinsCKXuCGlagovSRutherfordRB20. Persson J, Stavenow L, Wikstrand J, Israelsson B, Formgren J, Berglund G. Noninvasive quantification of atherosclerotic lesions: reproducibility of ultrasonographic measurement of arterial wall thickness and plaque size. Arterioscler Thromb. 1992;12(2):261-6.Noninvasive quantification of atherosclerotic lesions: reproducibility of ultrasonographic measurement of arterial wall thickness and plaque sizeArterioscler Thromb19922616212PerssonJStavenowLWikstrandJIsraelssonBFormgrenJBerglundG21. Touboul PJ, Elbaz A, Koller C, Lucas C, Adrai V, Chédru F, et al. Commom carotid artery intima-media thickness and brain infarction: the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC) case-control study. The GENIC Investigators. Circulation. 2000;102(3):313-8.Commom carotid artery intima-media thickness and brain infarction: the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC) case-control study. The GENIC InvestigatorsCirculation200031383102TouboulPJElbazAKollerCLucasCAdraiVChédruF22. Lorenz MW, von Kegler S, Steinmetz H, Markus HS, Sitzer M. Carotid intima-media thickening indicates a higher vascular risk across a wide age range. Prospective data from the carotid atherosclerosis progression study (CAPS). Stroke. 2006;37(1):87-92.Carotid intima-media thickening indicates a higher vascular risk across a wide age range: Prospective data from the carotid atherosclerosis progression study (CAPS)Stroke20068792137LorenzMWvon KeglerSSteinmetzHMarkusHSSitzerM23. Allan PL, Mowbray PI, Lee AJ, Fowkes GR. Relationship between carotid intima-media thickness and symptomatic and asymptomatic peripheral arterial disease: the Edinburgh Artery Study. Stroke. 1997;28(2):348-53.Relationship between carotid intima-media thickness and symptomatic and asymptomatic peripheral arterial disease: the Edinburgh Artery StudyStroke199734853228AllanPLMowbrayPILeeAJFowkesGR24. Simons PC, Algra A, Bots ML, Banga JD, Grobbee DE, van der Graaf Y. Common carotid intima-media thickness in patients with peripheral arterial disease or abdominal aortic aneurysm: the Smart Study. Atherosclerosis. 1999;146(2):243-8.Common carotid intima-media thickness in patients with peripheral arterial disease or abdominal aortic aneurysm: the Smart StudyAtherosclerosis199924382146SimonsPCAlgraABotsMLBangaJDGrobbeeDEvan der GraafY25. Sodhi HS, Shrestha SK, Rauniyar R, Rawat B. Prevalence of peripheral arterial disease by ankle-brachial index and its correlation with carotid intimal thickness and coronary risk factors in Nepalese population over the age of forty years. Kathmandu Univ Med J. 2007;5(1):12-5.Prevalence of peripheral arterial disease by ankle-brachial index and its correlation with carotid intimal thickness and coronary risk factors in Nepalese population over the age of forty yearsKathmandu Univ Med J200712515SodhiHSShresthaSKRauniyarRRawatB26. Burke GL, Evans GW, Riley WA, Sharrett AR, Howard G, Barnes RW, et al. Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) Study. Stroke. 1995;26(3):386-91.Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) StudyStroke199538691326BurkeGLEvansGWRileyWASharrettARHowardGBarnesRW27. Parv F, Tutelca A, Horhat R, Avram R, Balint M. Correlation between carotid intimal media thickness and ankle brachial index: comparison women versus men. Cercet Exp&Med-Chir. 2007:14(2-3):104-9.Correlation between carotid intimal media thickness and ankle brachial index: comparison women versus menCercet Exp& Med-Chir200710492-314ParvFTutelcaAHorhatRAvramRBalintM28. Keo HH, Baumgartner I, Hirsch AT, Duval S, Steg PG, Pasquet B, et al. Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease. Vasc Med. 2011;16(5):323-30.Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular diseaseVasc Med201132330516KeoHHBaumgartnerIHirschATDuvalSStegPGPasquetBOriginal ArticlesAssociation between ankle-brachial index and carotid atherosclerotic disease
BACKGROUND: The association between the ankle brachial index (ABI) and the measurement of intimal medial thickness (IMT) has not been fully studied. OBJECTIVE: We aimed to evaluate whether the prevalence of carotid atherosclerosis was higher in patients with ABI < 0.9 than in those with ABI > 0.9. METHODS: From January 2011 to December 2011, 118 patients (48 men and 70 women) were enrolled. ABI and IMT Measurements were performed in all patients. Patients were divided in Group 1 (ABI < 0.9) and Group 2 (ABI > 0.9) according to ABI values. Mann-Whitney, Chi-square and Fischer tests were used for comparison among the groups. Pearson's correlation was used to assess correlation between ABI and IMT. RESULTS: The prevalence of ABI < 0.9 was 29.7%, whereas carotid atherosclerosis > 1.5 mm was 34.7 %. Clinical characteristics were similar between groups 1 and 2: mean age (64 ± 9 vs. 62 ± 7.2 years, p = 0.1), male gender (40% vs. 41%, p = 0.9), hypertension (74% vs. 59%, p = 0.1), diabetes mellitus (54% vs. 35%, p = 0.051), dyslipidemia (26% vs. 24%, p = 0.8), smoking (57% vs. 65%, p = 0.4). The prevalence of carotid atherosclerosis was higher in group 1 (48.6% vs. 28.9%, p = 0.04). Pearson's correlation between ABI and IMT was -0.235, with a p value = 0.01. CONCLUSION: Patients with ABI < 0.9 showed a higher prevalence of carotid atherosclerosis. There was a negative correlation between ABI and IMT.
Augusto Cezar Lacerda Brasileiro; Dinaldo Cavalcanti de Oliveira; Edgar Guimarães Victor; Danielle A. G. Cavalcanti Oliveira; Laecio Leitão Batista
Hospital das Clínicas da UFPE, Recife, PE - Brasil
Mailing Address
ABSTRACT
BACKGROUND: The association between the ankle brachial index (ABI) and the measurement of intimal medial thickness (IMT) has not been fully studied.
OBJECTIVE: We aimed to evaluate whether the prevalence of carotid atherosclerosis was higher in patients with ABI < 0.9 than in those with ABI > 0.9.
METHODS: From January 2011 to December 2011, 118 patients (48 men and 70 women) were enrolled. ABI and IMT Measurements were performed in all patients. Patients were divided in Group 1 (ABI < 0.9) and Group 2 (ABI > 0.9) according to ABI values. Mann-Whitney, Chi-square and Fischer tests were used for comparison among the groups. Pearson's correlation was used to assess correlation between ABI and IMT.
RESULTS: The prevalence of ABI < 0.9 was 29.7%, whereas carotid atherosclerosis > 1.5 mm was 34.7 %. Clinical characteristics were similar between groups 1 and 2: mean age (64 ± 9 vs. 62 ± 7.2 years, p = 0.1), male gender (40% vs. 41%, p = 0.9), hypertension (74% vs. 59%, p = 0.1), diabetes mellitus (54% vs. 35%, p = 0.051), dyslipidemia (26% vs. 24%, p = 0.8), smoking (57% vs. 65%, p = 0.4). The prevalence of carotid atherosclerosis was higher in group 1 (48.6% vs. 28.9%, p = 0.04). Pearson's correlation between ABI and IMT was -0.235, with a p value = 0.01.
CONCLUSION: Patients with ABI < 0.9 showed a higher prevalence of carotid atherosclerosis. There was a negative correlation between ABI and IMT.
Atherosclerosis is a disease that affects the arterial system in a chronic and systemic way, caused by an inflammatory response together with immune reactions1. It occurs from the earliest stages of life, resulting from genetic predisposition and exposure to risk factors that cause endothelial dysfunction2,3.
Peripheral arterial disease (PAD) refers to atherosclerosis-induced alterations in the wall of the aorta and its branches, with the exception of the coronary arteries. The current concept of PAD is established by non-invasive tests, such as the ankle-brachial index (ABI) and the intima-media complex measurement (IMCM), even before the onset of any clinical symptoms4. The abnormal ABI indicates obstructive impairment of lower-limb arteries and is associated with risk of cardiovascular events (CVE), especially acute myocardial infarction (AMI) and cerebrovascular accident (CVA), regardless of other risk factors5-7.
Thickening of the carotid wall, diagnosed by B-mode ultrasound, represents a subclinical vascular alteration, which may progress to atherosclerosis. The numerical value of the IMCM of the carotid arteries is used for risk stratification of CVE8,9.
The measurements of the ABI and the intima-media complex (IMC) are low-cost, reproducible and have no associated risks. Both are considered as reference for the diagnosis of atherosclerosis. The ABI evaluates the involvement of the lower limbs, whereas the IMCM assesses carotid artery disease. The association between these measures is described, suggesting an inverse relationship and additionally, they can be used as independent markers for CVE10,11.
The primary objective of this study was to evaluate whether patients with ABI < 0.9 had a higher prevalence of carotid atherosclerosis when compared to those with index > 0.9. Secondary objectives were to analyze the association between ABI and IMC thickening, as well as verify possible correlations between the numerical values of ABI and the IMCM.
Methods
The study followed the ethical principles of the Declaration of Helsinki (WMA, 2000) and decree 196/96 of the National Health Council (CNS, 1996) and was approved by the Ethics Committee on Human Research of the institution, on April 20, 2011 according to protocol #426/2010.
Study design
Prospective, cross-sectional, analytical study with recruitment period set between May and December 2011.
Inclusion criteria
Patients aged 50 to 69 who were diabetic and/or smokers, or those older than 70 years regardless of risk factors, were included. All patients signed the informed consent form.
Exclusion criteria
Exclusion criteria were: advanced malignancy, percutaneous or surgical revascularization of lower limb arteries or carotid arteries, terminal liver disease, technical impossibility of measuring the ankle-brachial index or carotid intima-media complex, patients submitted to limb amputation and ABI > 1.4.
Study population
A total of 118 patients treated at the outpatient clinic specialized in cardiovascular surgery of a tertiary hospital and who met the inclusion criteria and had no exclusion criteria of the study were enrolled between April and December 2011.
Statistical Analysis
To compare the groups (ABI> 0.9 vs. ABI < 0.9) regarding qualitative variables, the Pearson's Chi-square test or Fisher's exact test were applied, when necessary. To compare the quantitative IMCM variables in the common carotid (IMCM-CC), in the internal carotid (IMCM-IC), in the external carotid (IMCM-EC) and overall (IMCM-OV), which was the maximum among all values, the nonparametric Mann-Whitney test was applied due to the non-normality of these variables. When quantitatively comparing ABI values with the measurements of intima-media complex in the carotid artery, a correlation analysis using Pearson's correlation coefficient was performed.
Statistical calculations were performed using SPSS for Windows release 18.0 - Statistical Package for the Social Sciences.
Ankle-brachial index protocol
ABI was measured using Doppler sonar equipment, model DV 610 (Medmega) and a sphygmomanometer with a 12-cm wide cuff, of which length varied from 29 to 40 cm. All measurements were performed with the patient in the supine position after 10 minutes of rest, and the systolic pressure of the posterior tibial artery, of the dorsalis pedis artery and brachial artery were measured bilaterally. We divided the highest pressure in the ankle by the highest systolic pressure found in the brachial artery of the upper limbs, thus obtaining the ABI12,13.
The normal values for the ABI are between 0.9 and 1.4. Thus, indices > 1.4 represent non-compression of arteries and an index < 0.9 demonstrate the presence of peripheral arterial disease (PAD)12.
Carotid intima-media complex measurement protocol
The measurement of intima-media complex was performed using ultrasound equipment model Medison X8 with a linear array transducer of 7.5 to 12 MHz. The common carotid artery was assessed bilaterally using automatic software (auto-IMT TM) and the internal and external carotid arteries were also assessed bilaterally through manual measurements.
The field depth was 30-40 mm. There was adjustment of gain with little intraluminal artifact, harmonic signals were not used and the cardiac cycle was monitored through ECG coupled to the image for verification at the end of diastole14-16.
A double line, representing the three layers of the arterial wall, was observed in the posterior wall of arteries. The first line is the interface between blood and the intima layer (anechoic lumen and echogenic intima), whereas the second line represents the interface between the media and adventitia layers (hypoechoic media and echogenic adventitia)17.
IMC thickening occurs between > 0.9 mm and < 1.5 mm, but when the measurement is > 1.5 mm, it is considered atherosclerotic plaque18.
Study flow chart
Patients were divided into 2 groups: group 1 comprised those who had ABI < 0.9 and group 2 had ABI > 0.9. The clinical variables, the IMCM and the prevalence of carotid plaque were compared between the groups. We tested the possibility of a linear correlation between the numerical values of the IMCM and the ABI.
For the purpose of analysis, we considered the IMCM of the common, internal and external carotid arteries. Measures of right and left were collected from each territory, but the highest value was considered for the statistical analysis. Maximum IMCM was defined as the highest value found, regardless of the carotid artery that was assessed.
Results
During the study period, 362 patients were treated at the vascular surgery outpatient clinic. Of these, 118 (32.5%) patients met the inclusion criteria and showed none of the exclusion criteria and were enrolled in the study. The prevalence of ABI < 0.9 was 29.7% (35 patients), whereas ABI > 0.9 was found in 70.3% of them (83 patients). The IMCM > 0.9 occurred in 69.5% of patients and carotid atherosclerotic plaque in 34.7% of them.
Table 1 shows there was no difference in the clinical profile between groups. However, the prevalence of ABI < 0.9 was higher in patients aged > 70 years (Table 2). The comparison between the groups showed that in group 1 (ABI < 0.9) IMCM was higher in the internal carotid [1.4 mm (max: 0.6 mm - min: 3.5 mm) vs. 1 mm (max: 0.5 mm - min: 3.8 mm), p = 0.04] and external carotid [0.7 mm (max: 0.5 mm - min: 3.2 mm) vs. 0.6 mm (max: 0.4 mm - min: 2.3 mm), p = 0.047]. The highest IMCM was observed in patients with ABI < 0.9 [1.4 mm (max: 0.7 mm - min: 3.5 mm) vs. 1 mm (max: 0.6 mm - min: 3.8 mm), p = 0.01) (Table 3).
The prevalence of atherosclerotic plaque was 48.6% (17 patients) in patients with ABI < 0.9 and 28.9% (24 patients) in those with ABI > 0.9 (p = 0.04). Pearson's correlation between ABI and maximum IMCM was - 0.234, with p value = 0.01 (Chart 1).
Discussion
Our study showed that patients with ABI < 0.9 had higher IMCM of internal and external carotid arteries, as well as the maximum value of the IMCM in the carotid territory. It is also noteworthy that the prevalence of carotid atherosclerosis was higher in patients with abnormal ABI.
The ABI is the product of a quantitative reduction in systolic blood pressure in the lower limbs caused by proximal atherosclerotic occlusion5. At first, it is thought that it occurs in the advanced stages of atherosclerosis. However, although the atherosclerotic disease is systemic, there are local vascular factors that may perhaps influence atheroma accumulation and vessel obstruction19. On the other hand, the thickening of the intima-media complex is considered a marker of premature atherosclerosis and a predictor of cardiovascular disease risk20-22. Serial temporal evaluations studies of ABI and IMCM values might explain several aspects of these tests, as well as atherosclerotic disease in peripheral vascular territories.
Researchers have studied the ABI and the IMCM and in this context, Allan et al23 evaluated 1,106 patients aged 55 to 74 years, included in the Edinburgh Artery Study and searched for associations between ABI and IMCM. They observed that the IMCM was higher in men and that older patients had higher intima-media complex values. There was a negative linear correlation between ABI and IMCM (r = - 0.116, p = 0.06). Patients with ABI < 0.9 had higher IMCM than those with ABI > 0.9 [0.87 mm (0.83 mm - 0.91 mm) vs. 0.8 mm (0.79 mm - 0.82 mm) p = 0.01]. In the subgroup of patients with claudication, the numerical values of the IMCM were higher [(0.90 mm (0.85 mm - 0.95 mm)]23.
Two other studies also showed that patients with ABI < 0.9 had higher IMCM when compared to those with ABI > 0.9 24,25. Our findings of higher IMCM in patients with ABI < 0.9 are consistent with the studies described above. However, our IMCM values were higher than those of the aforementioned studies and we believe that this fact is justified because we recruited patients with higher-risk clinical profile for advanced peripheral atherosclerotic disease.
It is noteworthy that according to the literature, patients with more advanced PAD, i.e. with claudication, had higher IMCM values than the general population26. We believe that patients with significant obstruction of the lower limb arteries have more advanced atherosclerosis and, therefore, have a greater chance of having higher IMCM and a higher prevalence of carotid plaque.
Two decades ago, the Rotterdam Study10, which included patients from the general population aged > 55 years, showed that the prevalence of ABI < 0.9 was 11.9% and that the increase of 0.1 mm in MCMI was associated with a reduction of 0.026 of the ABI and that patients with claudication had lower ABI values and higher values of IMCM, when compared to individuals without such symptoms.
Our study, in which the prevalence of abnormal ABI was 29.7%, showed a negative linear correlation between the IMCM and the numerical value of ABI. This finding supports the hypothesis suggested over 20 years ago by the researchers of the Rotterdam study.
The study by Parv et al27 had already found a negative linear correlation between ABI and the IMCM (r = - 0.157). However, our numerical "r" value of the correlation was higher and we believe that the severity of peripheral arterial disease in our group can be one of the factors that justify such finding.
Based on the concept that the ABI decreases with the progression of lower-limb proximal obstructions and IMCM increases with the progression of carotid atherosclerosis, one would expect to find a negative linear correlation between these two measures. This correlation was found in our study.
The literature shows only a suggestion of a negative linear correlation between ABI and IMCM23, and thus, it is possible that this is present only in certain subgroups of patients and/or phases of atherosclerosis. Therefore, we infer that such correlation may be present in patients with more advanced atherosclerosis.
When the IMCM value is > 1.5 mm, the atherosclerotic plaque is assumed to be present in the carotid arteries18. This finding is associated with an increased chance of myocardial infarction and CVA in these patients28. Patients with ABI < 0.9 in our study had a higher prevalence (close to 50%) of atherosclerotic plaque, when compared to those with normal ABI.
The main limitations of our study are: the need to choose a normal IMCM value, as there is no consensus in the literature; the absence of controls from the general population, which would allow the assessment of different stages of atherosclerosis; the lack of serial temporal assessment of ABI and IMCM; no possibility of probabilistic sample calculation, as there is no consensus on the prevalence of carotid atherosclerotic plaque diagnosed by Doppler ultrasound in diabetics and/or smokers with ABI < 0.9. It should be noted that it is possible, based on the prevalence rates of carotid atherosclerosis found in our study, to develop studies with similar sample size calculation.
Conclusions
Our study showed that the prevalence of PAD in the study population is high, which is consistent with the literature. In addition, ABI < 0.9 is related to the higher prevalence of thickening and atherosclerotic plaque in the carotid arteries and there is an inverse association between these two measures.