abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC São Paulo, SP, Brazil cBFdDdTysM5RsxSLRpVRHqB S0066-782X2013000600003 S0066-782X(13)10000600003 10.5935/abc.20130088 Artigos Originais Correlação dos escores de risco com a anatomia coronária na síndrome coronária aguda sem supra-ST Santos Elizabete Silva dos Aguiar Filho Luciano de Figueiredo Fonseca Daniela Menezes Londero Hugo José Xavier Rogério Martins Pereira Marcos Paulo Minuzzo Luiz Souza Roberta de Timerman Ari São Paulo São Paulo Instituto Dante Pazzanese de Cardiologia Brazil 06 2013 100 6 511 517 28 05 2012 19 11 2012 19 11 2012 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

FUNDAMENTO:Há poucas publicações sobre a correlação entre escores de risco e anatomia coronária na síndrome coronária aguda (SCA). OBJETIVO: Correlacionar os escores de risco com a gravidade da lesão coronária na SCA sem supra-ST. MÉTODOS: Foram analisados 582 pacientes entre julho de 2004 e outubro de 2006. Avaliou-se a correlação entre os escores de risco TIMI, GRACE hospitalar e em seis meses com lesão coronária > 50%, por método não paramétrico de Spearman. Modelo de regressão logística múltipla foi realizado para determinar a habilidade preditiva dos escores em discriminar quem terá ou não lesão coronária > 50%. RESULTADOS: Foram 319 (54,8%) homens e a média de idade era 59,9 (± 10,6) anos. Correlação positiva foi observada entre a pontuação dos escores de risco e lesão coronária > 50% (escore de risco TIMI r = 0,363 [p < 0,0001]; escore GRACE hospitalar r = 0,255 [p < 0,0001]; escore GRACE em seis meses r = 0,209 [< 0,0001]). A área sob a curva ROC de cada escore para discriminar quem terá ou não lesão coronária > 50% foi: TIMI = 0,704 [IC95% 0,656-0,752; p <0,0001]; GRACE hospitalar = 0,623 [IC 95% 0,573-0,673; p < 0,0001]; GRACE em seis meses = 0,562 [IC95% 0,510-0,613; p = 0,0255]. Na comparação entre as áreas sob a curva ROC, tem-se: TIMI versus GRACE hospitalar: p = 0,01; TIMI versus GRACE em seis meses: p < 0,0001; GRACE hospitalar versus GRACE em seis meses: p = 0,0461. CONCLUSÃO: Os escores de risco se correlacionam com a gravidade das lesões coronárias, sendo o escore de risco TIMI o que demonstrou melhor habilidade preditiva

 Fatores de Risco Vasos Coronários Síndrome Coronariana Aguda Prognóstico 19 04 2013

Correlação dos escores de risco com a anatomia coronária na síndrome coronária aguda sem supra-ST

Elizabete Silva dos Santos; Luciano de Figueiredo Aguiar Filho; Daniela Menezes Fonseca; Hugo José Londero; Rogério Martins Xavier; Marcos Paulo Pereira; Luiz Minuzzo; Roberta de Souza; Ari Timerman

Instituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brasil

Correspondência

RESUMO

FUNDAMENTO:Há poucas publicações sobre a correlação entre escores de risco e anatomia coronária na síndrome coronária aguda (SCA).

OBJETIVO: Correlacionar os escores de risco com a gravidade da lesão coronária na SCA sem supra-ST.

MÉTODOS: Foram analisados 582 pacientes entre julho de 2004 e outubro de 2006. Avaliou-se a correlação entre os escores de risco TIMI, GRACE hospitalar e em seis meses com lesão coronária > 50%, por método não paramétrico de Spearman. Modelo de regressão logística múltipla foi realizado para determinar a habilidade preditiva dos escores em discriminar quem terá ou não lesão coronária > 50%.

RESULTADOS: Foram 319 (54,8%) homens e a média de idade era 59,9 (± 10,6) anos. Correlação positiva foi observada entre a pontuação dos escores de risco e lesão coronária > 50% (escore de risco TIMI r = 0,363 [p < 0,0001]; escore GRACE hospitalar r = 0,255 [p < 0,0001]; escore GRACE em seis meses r = 0,209 [< 0,0001]). A área sob a curva ROC de cada escore para discriminar quem terá ou não lesão coronária > 50% foi: TIMI = 0,704 [IC95% 0,656-0,752; p <0,0001]; GRACE hospitalar = 0,623 [IC 95% 0,573-0,673; p < 0,0001]; GRACE em seis meses = 0,562 [IC95% 0,510-0,613; p = 0,0255]. Na comparação entre as áreas sob a curva ROC, tem-se: TIMI versus GRACE hospitalar: p = 0,01; TIMI versus GRACE em seis meses: p < 0,0001; GRACE hospitalar versus GRACE em seis meses: p = 0,0461.

CONCLUSÃO: Os escores de risco se correlacionam com a gravidade das lesões coronárias, sendo o escore de risco TIMI o que demonstrou melhor habilidade preditiva

Palavras-chave: Fatores de Risco, Vasos Coronários / anatomia & histologia, Síndrome Coronariana Aguda, Prognóstico.

Introdução

A doença cardíaca isquêmica é uma das principais causas de óbito no mundo. Segundo os dados do Heart Disease and Stroke Statistics, aproximadamente 2.300 norte-americanos morrem de doença cardiovascular por dia, e sua agudização sob a forma de síndrome coronária aguda (SCA) é a responsável pelo maior número.

Pacientes que se apresentam com SCA sem supra-ST (SST; infarto agudo do miocárdio sem SST ou angina instável) estão sob risco de eventos adversos, como morte ou infarto recorrente. Os escores de risco foram criados e são recomendados pelas diretrizes nacionais2 e internacionais3 para a identificação de pacientes com maior probabilidade para a ocorrência de eventos adversos, com recomendação para tratamento mais intensivo e cinecoronariografia precoce nessa população.

O escore de risco TIMI4 tem sua validade comprovada na predição de morte e eventos isquêmicos em pacientes com SCA sem SST. É composto por sete variáveis independentes relacionadas à ocorrência de morte, (re)infarto ou revascularização miocárdica (RM) urgente por isquemia recorrente em até 14 dias da apresentação, com a vantagem de ser facilmente calculável e reprodutível no mundo real.

Os escores de risco GRACE5,6(Global Registry of Acute Coronary Events), que foram desenvolvidos com base no banco de dados do registro GRACE, têm como objetivo apresentar um método simples e aplicável a todas as formas de SCA (com ou SST). O desfecho clínico foi, respectivamente, mortalidade por todas as causas, hospitalar ou em 180 dias, para o escore GRACE hospitalar e em seis meses.

Apesar do bom desempenho em discriminar quem terá ou não maior chance de eventos adversos, a literatura carece de estudos que demonstrem a correlação entre os escores e a magnitude das lesões coronárias à cinecoronariografia.

O objetivo desta pesquisa é avaliar a correlação entre os escores de risco TIMI, GRACE hospitalar e GRACE em seis meses com a gravidade das lesões coronárias à cinecoronariografia durante a internação em pacientes com SCA sem SST.

Métodos

População do estudo

Foram analisados prospectivamente 582 pacientes consecutivos com diagnóstico clínico de SCA sem SST admitidos de 1.º de julho de 2004 a 31 de outubro de 2006 submetidos à cinecoronariografia durante a internação, no pronto-socorro de um centro terciário em cardiologia. Os pacientes eram elegíveis se apresentassem idade igual ou superior a 18 anos e sintomas consistentes com isquemia coronária aguda dentro das últimas 48 horas. Foram excluídos aqueles com angina instável secundária, presença de alterações confundidoras do ECG da admissão (ritmo de marca-passo, fibrilação atrial, bloqueios de ramo), pacientes com suspeita de infarto com SST em evolução ou antecedente de cirurgia de revascularização miocárdica. Durante a internação, os pacientes foram acompanhados por meio de visitas médicas no pronto-socorro, na unidade coronária ou na enfermaria e, posteriormente, após a alta hospitalar em 14 e 180 dias, por contato telefônico, para verificação da presença ou não dos desfechos clínicos específicos de cada escore. Os escores de risco TIMI e GRACE (hospitalar e em seis meses) foram aplicados na população para os seus respectivos eventos adversos.

O comitê de ética em pesquisa local aprovou o protocolo do estudo, e todos os pacientes assinaram o Termo de Consentimento Livre e Esclarecido.

Cinecoronariografia

Para analisar a correlação entre os escores de risco e a anatomia coronária foram avaliadas lesões > 50% em tronco da coronária esquerda, coronária descendente anterior (ou em seus ramos diagonais), circunflexa (ou em seus ramos marginais) e coronária direita.

Análise estatística

A análise estatística foi feita por meio do programa SPSS for Windows versão 13,0 SPSS Institute, Chicago, Illinois.

As variáveis contínuas são descritas como médias ± desvio-padrão e as variáveis categóricas como frequências simples ou relativas.

Para avaliar a correlação entre a gravidade das lesões coronárias e os escores de risco TIMI, GRACE hospitalar e em seis meses, foi utilizado o método não paramétrico de Spearman7. Correlações foram consideradas significativas quando o nível descritivo do teste foi < 0,05 (p < 0,05).

A habilidade preditiva dos escores de risco em discriminar quem terá ou não possibilidade de lesão coronária > 50% foi determinada inicialmente pela análise univariada por meio do teste não paramétrico de Mann-Whitney7.Após a identificação de diferenças significativas dos escores entre os grupos com e sem lesão coronária > 50%, o poder preditivo independente dos escores foi avaliado pela estatística C (área sob a curva ROC)8Posteriormente, as estatísticas C dos escores de risco foram comparadas pela fórmula, onde r é o coeficiente de correlação entre as áreas9.

Resultados

Análise exploratória dos dados

Um total de 1.027 pacientes foi admitido com SCA sem SST no período. Destes, 734 foram submetidos à cinecoronariografia, pela qual foram excluídos da análise aqueles com antecedente de RM cirúrgica. Portanto, 582 pacientes corresponderam à população do estudo. Os dados da Tabela 1 trazem as características basais da população estudada.

Foram 319 homens (59,8%) e a média de idade foi de 59,8 anos (± 10,6). O fator de risco para doença arterial coronária mais frequente foi hipertensão arterial sistêmica, seguida de dislipidemia. Na internação, 179 pacientes (30,8%) apresentaram IAM sem SST; 383 pacientes (65,8%), angina instável III B; 20 pacientes (3,4%), angina instável III C da classificação de Braunwald10.

Os pacientes foram amplamente medicados com betabloqueador (92,4%), ácido acetilsalicílico (98,1%), nitroglicerina endovenosa (94,3%), antitrombínicos (89,8%), tienopiridínicos (90,5%), inibidor da enzima conversora da angiotensina (86,4%) e estatina (93,5%). A intervenção coronária percutânea (ICP) foi indicada em 199 pacientes (34,2%) e a cirurgia de RM em 104 (17,9%). O procedimento de revascularização miocárdica (cirurgia ou ICP) foi realizado durante a internação inicial em 263 pacientes (45,2%).

Durante a internação, 12 pacientes morreram (2,1%), o que correspondeu ao evento do escore de risco GRACE hospitalar, 54 (9,3%) apresentaram o evento composto do escore de risco TIMI em 14 dias(morte, [re]infarto ou RM urgente por isquemia recorrente)e 24 (4,1%) morreram em até 180 dias, correspondendo ao evento do escore de risco GRACE em seis meses.

Para cada paciente foi calculada a pontuação dos escores de risco TIMI, GRACE hospitalar e GRACE em seis meses. Nos dados da Tabela 2 observam-se as frequências simples e relativas dos principais achados da cinecoronariografia de 571 pacientes que tinham os dados completos.

Correlação positiva foi observada entre a pontuação dos escores de risco e lesão coronária > 50% (escore de risco TIMI r = 0,363 [p < 0,0001]; escore GRACE hospitalar r ;= ;0,255 [p < 0,0001]; escore GRACE em seis meses r ;= ;0,209 [p ;< ;0,0001]).

Na comparação entre a média da pontuação de cada escore de risco e a presença ou não de lesão coronária, observa-se que em todos os modelos de estratificação de risco a média da pontuação foi significativamente maior nos pacientes com pelo menos uma lesão coronária > 50% (Tabela 3).

Na análise de regressão logística múltipla, representada pela estatística C (área sob a curva ROC), foi determinada a habilidade preditiva dos escores de risco em discriminar quem terá ou não lesão coronária > 50% (estatística C: escore de risco TIMI = 0,704; intervalo de confiança [IC] 95% 0,656-0,752, p < 0,001; escore GRACE hospitalar ;= ;0,623; IC95% 0,573-0,673, p < 0,001; escore GRACE em seis meses ;= ;0,562; IC95% 0,510-0,613, p = 0,255)Gráfico 1.

Na comparação entre as áreas sob a curva ROC, tem-se: TIMI versus GRACE hospitalar: p = 0,0111; TIMI versus GRACE em seis meses: p < 0 ,0001; GRACE hospitalar versus GRACE em seis meses: p = 0,0461.

Discussão

Em decorrência da natureza heterogênea da população de pacientes com SCA sem SST, há ampla variação do risco para a ocorrência de óbito ou eventos isquêmicos recorrentes4,11-15. Pelo conhecimento mais profundo da fisiopatologia dessa síndrome, caminha-se para um refinamento e, portanto, melhor desempenho na avaliação prognóstica. Para a realização da estratificação de risco, dispõem-se, atualmente, de variáveis prognósticas independentes e dos modelos de estratificação de risco. O foco principal nessa estratégia é avaliar a probabilidade de ocorrência de eventos adversos, em especial morte ou (re)infarto, analisando dados da história clínica, do exame físico, do ECG e os marcadores de necrose miocárdica.

Na escolha dos desfechos clínicos, a não uniformidade entre os escores de risco atualmente disponíveis é considerada um fato importante, visto que para alguns modelos a mortalidade por todas as causas é analisada5,6 e outros incluem morte, infarto (reinfarto) ou RM urgente por isquemia recorrente4.

A importância da estratificação de risco está na avaliação inicial no pronto-socorro, tanto para liberação de pacientes com maior segurança como para admissão imediata daqueles de alto risco para realização dos cuidados médicos. Entre esses cuidados tem-se a incorporação de medidas mais intensivas, como a administração de medicamentos que apresentam maior risco de sangramento ou a estratégia invasiva precoce.

A realização de cinecoronariografia nos pacientes de mais alto risco objetiva determinar aqueles que são passíveis de procedimentos de RM (ICP ou cirurgia). Apesar disso, a estratificação de risco, utilizando as variáveis independentes ou os modelos de estratificação de risco, não tem como meta avaliar a gravidade da anatomia coronária. Para esse fim, pouco se tem divulgado na literatura sobre a correlação entre os escores de risco e a extensão ou a gravidade da doença arterial coronária.

Muitas variáveis independentes de pior prognóstico se correlacionam com obstrução arterial coronária mais grave. Entre as variáveis clínicas, os pacientes idosos com doença arterial coronária apresentam lesões mais graves em comparação com pacientes mais jovens e experimentam resultados mais desfavoráveis16. O diabetes melito é considerado o maior fator de risco para morbidade e mortalidade cardiovascular17, levando a uma chance 3-5 vezes maior de desenvolvimento de doença arterial coronária18.

Da mesma forma, o tipo de procedimento de RM prévia é um marcador da gravidade da doença arterial coronária. Em pacientes submetidos a ICP prévia, a doença arterial coronária subjacente é menos acentuada. Naqueles com cirurgia de RM, disfunção ventricular esquerda ou doença de múltiplos vasos é encontrada com mais constância. Consequentemente, pacientes com ICP apresentam prognóstico mais favorável19.

Suspeita de SCA, com marcada inversão simétrica das ondas T em parede precordial, sugere isquemia aguda, particularmente em decorrência de estenose crítica da artéria coronária descendente anterior20.

Adicionalmente, lesões envolvendo maior número de vasos estão presentes em pacientes com troponina positiva em comparação com aqueles com troponina negativa21.

Acredita-se que estimar a possível gravidade das lesões coronárias antes de realizar a cinecoronariografia pode colaborar para decisões terapêuticas mais adequadas22. Por exemplo, naqueles com alta probabilidade de apresentar lesões coronárias passíveis de cirurgia de RM, pode-se não administrar tienopirídinicos antes da realização da cinecoronariografia.

Garcia e cols.22 avaliaram a correlação entre o escore de risco TIMI e a gravidade da doença arterial coronária em 688 pacientes com SCA sem SST submetidos à cinecoronariografia. Foram excluídos os pacientes com antecedentes de cirurgia de RM ou ICP recente. Os autores concluíram que, para cada aumento na categoria de risco, há aumento não apenas na porcentagem de eventos adversos, mas também na probabilidade de pacientes com doença de três vasos ou com lesão de tronco da coronária esquerda. Diferentemente de nosso trabalho, os dados desse estudo foram limitados à análise retrospectiva pela qual foi avaliado exclusivamente o escore de risco TIMI.

Da mesma forma, para explorar as bases fisiopatológicas das variáveis do escore de risco TIMI, Mega e cols.23 analisaram a relação entre esse modelo de estratificação de risco e a anatomia coronária em 1.491 pacientes com SCA sem SST incluídos no ensaio clínico PRISM-PLUS24.Pacientes com escores de risco 5-7 (alto risco) apresentaram mais comumente estenose grave e doença multiarterial, comparados com aqueles com escores de risco 0-2 (baixo risco). Probabilidade de lesão em tronco de coronária esquerda, presença de trombo intracoronário e redução do fluxo em lesão culpada foram progressivamente maiores com o aumento da pontuação do escore de risco. História prévia de doença arterial coronária, idade avançada e desvio do segmento ST foram as variáveis do escore de risco TIMI que apresentaram a mais importante associação com a gravidade da lesão arterial coronária. Por outro lado, elevação dos biomarcadores de necrose miocárdica, desvio do segmento ST e uso prévio de aspirina emergiram com importante correlação com trombo intracoronário e/ou redução do fluxo da artéria coronária culpada. Os dados desse estudo explicam em parte o benefício particular de antitrombóticos entre os pacientes de mais alto risco.

Recentemente, Ben Salem e cols.25 avaliaram a extensão e a gravidade da lesão arterial coronária em análise retrospectiva de 239 pacientes com SCA sem SST. Os autores classificaram os pacientes em baixo, intermediário e alto risco pelo escore de risco TIMI e compararam os achados angiográficos entre os três grupos. Foi observado que pacientes com escores de risco 0-2 apresentavam mais significativamente angiografia coronária normal ou doença arterial coronária insignificante, em comparação aos de escore 5-7 (36,3% versus 13%, p ;< ;0,001). Por outro lado, doença de três vasos ou lesão de tronco da coronária esquerda foi mais frequentemente encontrada entre pacientes de alto risco. Os autores concluíram que o escore de risco TIMI se correlacionou com doença arterial mais grave.

Em nosso estudo avaliamos uma população de 582 pacientes com SCA sem SST, com características bem representativas do mundo real. Com o objetivo de analisar a correlação entre os escores de risco atualmente recomendados pelas diretrizes e a presença de lesão arterial coronária mais grave, este corresponde ao primeiro estudo no qual foram avaliados simultaneamente três modelos de estratificação em uma mesma população.

Nos três escores de risco analisados, a média da pontuação foi significativamente maior nos pacientes com lesão arterial coronária mais grave, promovendo dessa forma uma validação dos modelos para discriminar aqueles com doença arterial coronária mais importante. Com esse resultado optou-se por realizar uma análise de regressão logística múltipla para avaliar a habilidade independente de cada escore para a presença ou não de lesão coronária > 50%.

No cálculo da estatística C (área sob a curva ROC) observa-se que o escore de risco TIMI apresenta melhor desempenho. Isso foi comprovado por meio da comparação entre as áreas sob a curva ROC dos três modelos. O escore de risco TIMI apresentou melhor habilidade em discriminar quem terá ou não lesão coronária > 50%, sendo superior aos escores GRACE. O escore GRACE hospitalar, por sua vez, foi superior ao escore de risco GRACE em seis meses.

Limitações

Este estudo apresenta limitações. Os resultados se aplicam apenas a pacientes com SCA sem SST que foram encaminhados para angiografia, não podendo ser aplicados, portanto, a todos os pacientes com SCA. A população estudada foi considerada em um único centro, podendo ser cogitado que não poderia ser feita a inferência dos resultados para o mundo real de outros centros.

Conclusão

Os escores de risco TIMI, GRACE hospitalar e GRACE em seis meses se correlacionam com a gravidade das lesões coronárias à cinecoronariografia. O escore de risco TIMI foi o que demonstrou melhor habilidade preditiva para discriminar quem terá ou não possibilidade de lesão coronária > 50%.

Referências

1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Heart disease and stroke statistics - 2010 update: a report from the American Heart Association. Circulation. 2010;121(7):e46-e215. Erratum in: Circulation. 2010 Mar 30;121(12):e260. Stafford, Randall [corrected to Roger, Véronique L]. Circulation. 2011 Oct 18;124(16):e425.

2. Nicolau JC, Timerman A, Piegas LS, Marin-Neto JA, Rassi A Jr. [Guidelines for Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction of the Brazilian Society of Cardiology (II Edition, 2007)]. Arq Bras Cardiol. 2007;89(4):e89-131.

3. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey Jr DE, et al. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007;116(7):e148-304.

4. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-42.

5. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163(19):2345-53.

6. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA. 2004;291(22):2727-33.

7. Siegel S, Castellan NJ. Nonparametric statistics. 2nd ed. New York: McGraw-Hill; 1988.

8. Fletcher RH, Fletcher SW, Wagner EH. Epidemiologia clínica - bases científicas da conduta médica. 2ª ed. Porto Alegre: Artes Médicas; 2009.

9. Hanley JA, McNeil BI. A method of comparing the areas under receive operating characteristic curves derived from the same cases. Radiology. 1983;148(3):839-43.

10. Braunwald E. Unstable angina: an etiologic approach to management. Circulation. 1998;98(21):2219-22.

11. Farhi JI, Cohen M, Fuster V. The broad spectrum of unstable angina pectoris and its implications for future controlled trials. Am J Cardiol. 1986;58(6):547-50.

12. Braunwald E, Mark DB, Jones RH, Brown J, Brown L, Cheitlin MD, et al. Unstable angina: diagnosis and management. Rockville (MD): Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, Public Health Service, US Department of Health and Human Services; 1994. (Clinical Practice Guideline, nº 10).

13. Calvin JE, Klein LW, VandenBerg BJ, Meyer P, Condon JV, Snell RJ, et al. Risk stratification in unstable angina: prospective validation of the Braunwald classification. JAMA. 1995;273(2):136-41.

14. Armstrong PW, Fu Y, Chang WC, Topol EJ, Granger CB, Betriu A, et al. Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia. The GUSTO-IIb Investigators. Circulation. 1998;98(18):1860-8.

15. Zaacks SM, Liebson PR, Calvin JE, Parrillo JE, Klein LW. Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J Am Coll Cardiol. 1999;33(1):107-18.

16. Stone PH, Thompson B, Anderson HV, Kronenberg MW, Gibson RS, Rogers WJ, et al. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry. JAMA. 1996;275(14):1104-12.

17. Stone PH, Thompson B, Anderson HV, Kronenberg MW, Gibson RS, Rogers WJ, et al. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry. JAMA. 1996;275(14):1104-12.

18. Roffi M, Chew DP, Mukherjee D, Bhatt DL, White JA, Heeschen C, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation. 2001;104(23):2767-71.

19. Bierman EL. George Lyman Duff Memorial Lecture. Atherogenesis in diabetes. Arterioscler Thromb. 1992;12(6):647-56.

20. Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation. 2000;101(22):2557-67.

21. de Zwaan C, Bär FW, Janssen JH, Cheriex EC, Dassen WR, Brugada P, et al. Angiographic and clinical characteristics of patients with unstable angina showing an ECG pattern indicating critical narrowing of the proximal LAD coronary artery. Am Heart J. 1989;117(3):657-65.

22. Newby LK, Kaplan AL, Granger BB, Sedor F, Califf RM, Ohman EM. Comparison of cardiac troponin T versus creatine kinase-MB for risk stratification in a chest pain evaluation unit. Am J Cardiol. 2000;85(7):801-5.

23. Garcia S, Canoniero M, Peter A, de Marchena E, Ferreira A. Correlation of TIMI risk score with angiographic severity and extent of coronary artery disease in patients with non-ST-elevation acute coronary syndromes. Am J Cardiol. 2004;93(7):813-6.

24. Mega JL, Morrow DA, Sabatine MS, Zhao XQ, Snapinn SM, DiBattiste PM, et al. Correlation between the TIMI risk score and high-risk angiographic findings in non-ST-elevation acute coronary syndromes: observations from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial. Am Heart J. 2005;149(5):846-50.

25. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med. 1998;338:1488-97. Erratum in N Engl J Med 1998 Aug 6;339(6):415.

26. Ben Salem H, Ouali S, Hammas S, Bougmiza I, Gribaa R, Ghannem K, et al. [Correlation of TIMI risk score with angiographic extent and severity of coronary artery disease in non-ST-elevation acute coronary syndromes]. Ann Cardiol Angeiol (Paris). 2011;60(2):87-91.

Elizabete Silva dos Santos

Rua das Rosas, 126 / 32, Mirandópolis, CEP 04048-000, São Paulo, SP - Brasil

E-mail:

elizabetessantos@cardiol.br,

elizabetessantos@bol.com.br

Artigo recebido em 28/05/12, revisado em 19/11/12, aceito em 19/11/12.

1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Heart disease and stroke statistics - 2010 update: a report from the American Heart Association. Circulation. 2010;121(7):e46-e215. Erratum in: Circulation. 2010 Mar 30;121(12):e260. Stafford, Randall [corrected to Roger, Véronique L]. Circulation. 2011 Oct 18;124(16):e425. Heart disease and stroke statistics - 2010 update: a report from the American Heart Association Circulation 2010 e46 e215 7 121 Lloyd-Jones D Adams RJ Brown TM Carnethon M Dai S De Simone G Circulation 2010 30 03 12 121 Circulation 2011 18 10 16 124 2. Nicolau JC, Timerman A, Piegas LS, Marin-Neto JA, Rassi A Jr. [Guidelines for Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction of the Brazilian Society of Cardiology (II Edition, 2007)]. Arq Bras Cardiol. 2007;89(4):e89-131. Guidelines for Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction of the Brazilian Society of Cardiology (II Edition, 2007) Arq Bras Cardiol 2007 e89 131 4 89 Nicolau JC Timerman A Piegas LS Marin-Neto JA Rassi A Jr 3. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey Jr DE, et al. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007;116(7):e148-304. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine Circulation 2007 e148 304 7 116 Anderson JL Adams CD Antman EM Bridges CR Califf RM Casey Jr DE 4. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-42. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making JAMA 2000 835 42 7 284 Antman EM Cohen M Bernink PJ McCabe CH Horacek T Papuchis G 5. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163(19):2345-53. Predictors of hospital mortality in the global registry of acute coronary events Arch Intern Med 2003 2345 53 19 163 Granger CB Goldberg RJ Dabbous O Pieper KS Eagle KA Cannon CP 6. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA. 2004;291(22):2727-33. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry JAMA 2004 2727 33 22 291 Eagle KA Lim MJ Dabbous OH Pieper KS Goldberg RJ 7. Siegel S, Castellan NJ. Nonparametric statistics. 2nd ed. New York: McGraw-Hill; 1988. Nonparametric statistics 1988 Siegel S Castellan NJ 8. Fletcher RH, Fletcher SW, Wagner EH. Epidemiologia clínica - bases científicas da conduta médica. 2Ş ed. Porto Alegre: Artes Médicas; 2009. Epidemiologia clínica - bases científicas da conduta médica 2009 Fletcher RH Fletcher SW Wagner EH 9. Hanley JA, McNeil BI. A method of comparing the areas under receive operating characteristic curves derived from the same cases. Radiology. 1983;148(3):839-43. A method of comparing the areas under receive operating characteristic curves derived from the same cases Radiology 1983 839 43 3 148 Hanley JA McNeil BI 10. Braunwald E. Unstable angina: an etiologic approach to management. Circulation. 1998;98(21):2219-22. Unstable angina: an etiologic approach to management Circulation 1998 2219 22 21 98 Braunwald E 11. Farhi JI, Cohen M, Fuster V. The broad spectrum of unstable angina pectoris and its implications for future controlled trials. Am J Cardiol. 1986;58(6):547-50. The broad spectrum of unstable angina pectoris and its implications for future controlled trials Am J Cardiol 1986 547 50 6 58 Farhi JI Cohen M Fuster V 12. Braunwald E, Mark DB, Jones RH, Brown J, Brown L, Cheitlin MD, et al. Unstable angina: diagnosis and management. Rockville (MD): Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, Public Health Service, US Department of Health and Human Services; 1994. (Clinical Practice Guideline, nş 10). Unstable angina: diagnosis and management 1994 Braunwald E Mark DB Jones RH Brown J Brown L Cheitlin MD 13. Calvin JE, Klein LW, VandenBerg BJ, Meyer P, Condon JV, Snell RJ, et al. Risk stratification in unstable angina: prospective validation of the Braunwald classification. JAMA. 1995;273(2):136-41. Risk stratification in unstable angina: prospective validation of the Braunwald classification JAMA 1995 136 41 2 273 Calvin JE Klein LW VandenBerg BJ Meyer P Condon JV Snell RJ 14. Armstrong PW, Fu Y, Chang WC, Topol EJ, Granger CB, Betriu A, et al. Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia. The GUSTO-IIb Investigators. Circulation. 1998;98(18):1860-8. Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia. The GUSTO-IIb Investigators Circulation 1998 1860 8 18 98 Armstrong PW Fu Y Chang WC Topol EJ Granger CB Betriu A 15. Zaacks SM, Liebson PR, Calvin JE, Parrillo JE, Klein LW. Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J Am Coll Cardiol. 1999;33(1):107-18. Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J Am Coll Cardiol 1999 107 18 1 33 Zaacks SM Liebson PR Calvin JE Parrillo JE Klein LW 16. Stone PH, Thompson B, Anderson HV, Kronenberg MW, Gibson RS, Rogers WJ, et al. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry. JAMA. 1996;275(14):1104-12. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry JAMA 1996 1104 12 14 275 Stone PH Thompson B Anderson HV Kronenberg MW Gibson RS Rogers WJ 18. Roffi M, Chew DP, Mukherjee D, Bhatt DL, White JA, Heeschen C, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation. 2001;104(23):2767-71. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes Circulation 2001 2767 71 23 104 Roffi M Chew DP Mukherjee D Bhatt DL White JA Heeschen C 19. Bierman EL. George Lyman Duff Memorial Lecture. Atherogenesis in diabetes. Arterioscler Thromb. 1992;12(6):647-56. George Lyman Duff Memorial Lecture: Atherogenesis in diabetes Arterioscler Thromb 1992 647 56 6 12 Bierman EL 20. Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation. 2000;101(22):2557-67. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation: Results from an international trial of 9461 patients. The PURSUIT Investigators Circulation 2000 2557 67 22 101 Boersma E Pieper KS Steyerberg EW Wilcox RG Chang WC Lee KL 21. de Zwaan C, Bär FW, Janssen JH, Cheriex EC, Dassen WR, Brugada P, et al. Angiographic and clinical characteristics of patients with unstable angina showing an ECG pattern indicating critical narrowing of the proximal LAD coronary artery. Am Heart J. 1989;117(3):657-65. Angiographic and clinical characteristics of patients with unstable angina showing an ECG pattern indicating critical narrowing of the proximal LAD coronary artery Am Heart J 1989 657 65 3 117 de Zwaan C Bär FW Janssen JH Cheriex EC Dassen WR Brugada P 22. Newby LK, Kaplan AL, Granger BB, Sedor F, Califf RM, Ohman EM. Comparison of cardiac troponin T versus creatine kinase-MB for risk stratification in a chest pain evaluation unit. Am J Cardiol. 2000;85(7):801-5. Comparison of cardiac troponin T versus creatine kinase-MB for risk stratification in a chest pain evaluation unit Am J Cardiol 2000 801 5 7 85 Newby LK Kaplan AL Granger BB Sedor F Califf RM Ohman EM 23. Garcia S, Canoniero M, Peter A, de Marchena E, Ferreira A. Correlation of TIMI risk score with angiographic severity and extent of coronary artery disease in patients with non-ST-elevation acute coronary syndromes. Am J Cardiol. 2004;93(7):813-6. Correlation of TIMI risk score with angiographic severity and extent of coronary artery disease in patients with non-ST-elevation acute coronary syndromes Am J Cardiol 2004 813 6 7 93 Garcia S Canoniero M Peter A de Marchena E Ferreira A 24. Mega JL, Morrow DA, Sabatine MS, Zhao XQ, Snapinn SM, DiBattiste PM, et al. Correlation between the TIMI risk score and high-risk angiographic findings in non-ST-elevation acute coronary syndromes: observations from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial. Am Heart J. 2005;149(5):846-50. Correlation between the TIMI risk score and high-risk angiographic findings in non-ST-elevation acute coronary syndromes: observations from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial Am Heart J 2005 846 50 5 149 Mega JL Morrow DA Sabatine MS Zhao XQ Snapinn SM DiBattiste PM 25. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med. 1998;338:1488-97. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction: Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators N Engl J Med 1998 1488 97 338 Erratum in N Engl J Med 1998 Aug 6;339(6):415. N Engl J Med 1998 06 08 339 26. Ben Salem H, Ouali S, Hammas S, Bougmiza I, Gribaa R, Ghannem K, et al. [Correlation of TIMI risk score with angiographic extent and severity of coronary artery disease in non-ST-elevation acute coronary syndromes]. Ann Cardiol Angeiol (Paris). 2011;60(2):87-91. Correlation of TIMI risk score with angiographic extent and severity of coronary artery disease in non-ST-elevation acute coronary syndromes Ann Cardiol Angeiol (Paris) 2011 87 91 2 60 Ben Salem H Ouali S Hammas S Bougmiza I Gribaa R Ghannem K Original Articles Correlation of risk scores with coronary anatomy in non-ST-elevation acute coronary syndrome

BACKGROUND: The literature lacks studies regarding the correlation between risk scores and coronary anatomy in acute coronary syndrome (ACS) OBJECTIVE: Correlate risk scores with the severity of the coronary lesion in ACS with non-ST elevation. METHODS: A total of 582 patients were analyzed between July 2004 and October 2006. The correlation between TIMI risk scores and GRACE (hospital and six months) scores was performed for patients with coronary lesion > 50%, using Spearman´s non-parametric method. Multiple regression logistics was used to determine the predictive ability of the scores to discriminate to discriminate who will have a coronary lesion > 50%. RESULTS: Most subjects were male (319 or 54.8%), mean age of 59.9 (± 10.6) years. A positive correlation was observed between risk scores and >coronary lesion > 50% (TIMI r = 0.363 [p < 0.0001]; hospital GRACE r = 0.255 [p < 0.0001]; GRACE at six months r = 0.209 [< 0.0001]). The area under the ROC curve for each score to determine to discriminate who will have a coronary lesion > 50% was: TIMI = 0.704 [CI95% 0.656-0.752; p <0.0001]; hospital GRACE = 0.623 [CI95% 0.573-0.673; p < 0.0001]; GRACE at six months= 0.562 [CI95% 0.510-0.613; p ;= 0.0255]. Comparing the areas under the ROC curve, it was found: TIMI versus hospital GRACE: p = 0.01; TIMI versus GRACE at six months:p < 0.0001; hospital GRACE versus GRACE at six months: p = 0.0461. CONCLUSION: Risk scores correlate with the severity of coronary lesions, and the TIMI risk score showed the best predictive ability.

 Risk Factors Coronary Vessels Acute Coronary Syndrome Prognosis

Elizabete Silva dos Santos; Luciano de Figueiredo Aguiar Filho; Daniela Menezes Fonseca; Hugo José Londero; Rogério Martins Xavier; Marcos Paulo Pereira; Luiz Minuzzo; Roberta de Souza; Ari Timerman

Instituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brazil

Mailing Address

ABSTRACT

BACKGROUND: The literature lacks studies regarding the correlation between risk scores and coronary anatomy in acute coronary syndrome (ACS).

OBJECTIVE: Correlate risk scores with the severity of the coronary lesion in ACS with non-ST elevation.

METHODS: A total of 582 patients were analyzed between July 2004 and October 2006. The correlation between TIMI risk scores and GRACE (hospital and six months) scores was performed for patients with coronary lesion > 50%, using Spearman´s non-parametric method. Multiple regression logistics was used to determine the predictive ability of the scores to discriminate to discriminate who will have a coronary lesion > 50%.

RESULTS: Most subjects were male (319 or 54.8%), mean age of 59.9 (± 10.6) years. A positive correlation was observed between risk scores and >coronary lesion > 50% (TIMI r = 0.363 [p < 0.0001]; hospital GRACE r = 0.255 [p < 0.0001]; GRACE at six months r = 0.209 [< 0.0001]). The area under the ROC curve for each score to determine to discriminate who will have a coronary lesion > 50% was: TIMI = 0.704 [CI95% 0.656-0.752; p <0.0001]; hospital GRACE = 0.623 [CI95% 0.573-0.673; p < 0.0001]; GRACE at six months= 0.562 [CI95% 0.510-0.613; p ;= 0.0255]. Comparing the areas under the ROC curve, it was found: TIMI versus hospital GRACE: p = 0.01; TIMI versus GRACE at six months:p < 0.0001; hospital GRACE versus GRACE at six months: p = 0.0461.

CONCLUSION: Risk scores correlate with the severity of coronary lesions, and the TIMI risk score showed the best predictive ability

Keywords: Risk Factors; Coronary Vessels / anatomy & histology; Acute Coronary Syndrome; Prognosis.

Introduction

Ischemic heart disease is a leading cause of death worldwide. According to data from the Heart Disease and Stroke Statistics1 approximately 2,300 North Americans die of cardiovascular disease each day, with acute coronary syndrome (ACS) being responsible for the largest number.

Patients presenting with non-ST elevation ACS (STE; acute myocardial infarction without STE or unstable angina) are at risk for adverse events such as death or recurrent infarction. The risk scores were created and are recommended by national2 and international3 guidelines to identify patients with a higher probability for the occurrence of adverse events, with a recommendation for more intensive treatment and early cineradiography in this population.

The TIMI4 risk score has proven its validity in predicting death and ischemic events in patients with non-ST elevation ACS. It is comprised of seven independent variables related to the occurrence of death, (re)infarction or urgent myocardial revascularization (MR) due to recurrent ischemia within 14 days from its calculation, with the advantage of being easily calculable and reproducible in the real world.

The GRACE5,6 (Global Registry of Acute Coronary Events) risk scores, which were developed based on the GRACE registry database, aim to provide a simple and applicable risk score for all forms of ACS (with or without ST elevation). The clinical outcomes were, respectively, all-cause mortality or hospitalization within 180 days for the GRACE hospital score, which was applicable for up to six months.

Despite good performance in discriminating which patients are most likely to experience an adverse event, the literature lacks studies that demonstrate the correlation between the scores and the magnitude of coronary lesions found by coronary angiography.

The objective of this research is to evaluate the correlation between TIMI risk score, hospital GRACE score and GRACE score at six months with the severity of coronary lesions found by coronary angiography during hospitalization in patients with non-ST elevation ACS.

Methods

Study Population

A prospective analysis of 582 consecutive patients with the clinical diagnosis of non-ST elevation ACS admitted from July 1, 2004 to October 31, 2006 was performed; the patients had undergone coronary angiography during hospitalization, after presenting to the emergency room of a tertiary cardiology center. Patients were eligible if they were age 18 years or older and had symptoms consistent with acute coronary ischemia within the last 48 hours. We excluded those with unstable secondary angina, those with confounding ECG changes on admission (pacemaker rhythm, atrial fibrillation, and bundle branch blocks), patients with suspected evolving infarction or those who had had previous coronary artery bypass surgery. During hospitalization, patients were followed up by medical visits in the emergency room, on the coronary care unit or on the ward and, after being discharged, they were contacted within 14 and 180 days by telephone to verify the presence of any specific outcomes pertinent to each score. The TIMI risk scores and GRACE (hospital and six months) scores were applied to the population to determine their risk of adverse events.

The local research ethics committee approved the study protocol, and all patients signed an informed consent form.

Coronary Angiography

To analyze the correlation between risk scores and coronary anatomy, lesions were considered if > 50% in the left main coronary artery, anterior descending coronary artery (or its diagonal branches), circumflex artery (or in its marginal branches) and right coronary artery.

Statistical Analysis

The statistical analysis was performed using SPSS for Windows version 13.0 (SPSS Institute, Chicago, Illinois).

Continuous variables are reported as mean ± standard deviations and categorical variables as simple or relative frequencies.

To evaluate the correlation between the severity of coronary lesions and TIMI risk scores, GRACE hospital and 6 month scores, we used the Spearman nonparametric method7.

The predictive ability of risk scores to discriminate who will have a coronary lesion > 50% was determined initially by univariate analysis using the nonparametric Mann-Whitney test7. Following the identification of significant differences in scores between the groups with and without coronary lesion > 50%, the predictive power (irrespective of scores) was evaluated using the C statistic (area under the ROC curve)8. Subsequently, the C statistic of the risk scores were compared using the formula where r is the correlation coefficient between the areas9.

Results

Exploratory data analysis

One thousand and twenty seven (1,027) patients were admitted with non-ST elevation ACS in the study period. Of these, 734 underwent coronary angiography, excluding from analysis those with previous surgical MR. Therefore, 582 patients were included in the study population. The data in Table 1 includes the baseline characteristics of the study population.

There were 319 men (59.8%) and the mean age was 59.8 years (± 10.6). The most frequent risk factor for coronary arterial disease was systemic arterial hypertension, followed by dyslipidemia. Upon admission, 179 patients (30.8%) had non-ST elevation acute myocardial infarction, 383 patients (65.8%) had unstable angina class III B and 20 patients (3.4%) had unstable angina of Braunwald's III C classification10.

The patients were medicated with beta-blockers (92.4%), acetylsalicylic acid (98.1%), intravenous nitroglycerin (94.3%), antithrombins (89.8%), thienopyridines (90.5%), angiotensin converting enzyme (ACE) inhibitors (86.4%) and statins (93.5%). Percutaneous coronary intervention (PCI) was performed in 199 patients (34.2%) and MR in 104 patients (17.9%). The procedure for myocardial revascularization (surgery or PCI) was performed during the initial hospitalization in 263 patients (45.2%).

During hospitalization, 12 patients died (2.1%), which corresponded to the risk hospital GRACE score, 54 (9.3%) experienced the compound event of the TIMI risk score within 14 days (death, [re ]infarction or urgent MR due to recurrent ischemia) and 24 (4.1%) died within six months, corresponding to the GRACE risk score event within six months.

For each patient, TIMI, hospital GRACE risk score and GRACE risk score for six months was calculated. Table 2 shows the absolute and relative frequencies of the main findings of coronary angiography in 571 patients who had complete data.

A positive correlation was observed between the risk scores and coronary lesions > 50% (TIMI risk score r = 0.363 [p <0.0001 ]; hospital GRACE score r = 0.255 [p <0.0001 ]; and GRACE score in six months r = 0.209 [p < 0.0001 ]).

When comparing the mean score of each risk score with the presence or absence of coronary lesion, it is observed that in all risk stratification models the mean score was significantly higher in patients with at least one coronary lesion > 50% (Table 3).

In multiple logistic regression analysis, represented by the C statistic (area under the ROC curve), the predictive ability of risk scores to discriminate who will have a coronary lesion > 50% (C statistic: TIMI risk score = 0.704, confidence interval [CI ] 95% from 0.656 to 0.752, p < 0.001; hospital GRACE score = 0.623, 95% CI 0.573 to 0.673, p < 0.001; GRACE score in six months = 0.562, 95% CI 0.510 - 0.613, p = 0.255) was determined - (Chart 1).

Comparing the areas under the ROC curve, we have: TIMI versus hospital GRACE score: p = 0.0111; TIMI versus GRACE score in six months: p < 0, 0001; hospital GRACE score versus GRACE score in six months: p = 0.0461.

Discussion

Due to the heterogeneous nature of the population of patients with non-ST elevation ACS, there is wide variation in terms of risk for the occurrence of death or recurrent ischemic events4,11-15. From the deepest knowledge of the physiopathology of this syndrome, one moves toward refinement and, therefore, better performance in prognostic evaluation. To perform risk stratification, one has current independent prognostic variables and models of risk stratification. The main focus of this strategy is to evaluate the probability of occurrence of adverse events, particularly death or (re)infarction, analyzing data from the clinical history, physical examination, ECG and markers of myocardial necrosis.

In determining clinical outcomes, the non-uniformity among the currently available risk scores is considered an important factor, since for some models mortality from all causes is analyzed5,6 while others include death, myocardial infarction (reinfarction) or urgent MR due to recurrent ischemia4.

The importance of risk stratification becomes evident in the initial evaluation of the patient in the emergency ward, both for discharging patients safely and for immediate admission of those who are at high risk and require immediate medical care. Among medical strategies, one must choose between the incorporation of more intensive measures, such as the administration of drugs that carry a higher risk of bleeding, or early invasive strategy.

Coronary angiography in patients at highest risk objectively determines those who are likely to have MR procedures (PCI or surgery). Nevertheless, risk stratification, using independent variables or models of risk stratification, does not have the ability to assess the severity of coronary anatomy. To that end, little has been published in the literature regarding the correlation between risk scores and the extent or severity of coronary artery disease.

Many independent variables with poor prognosis are correlated with severe arterial obstruction. Among the clinical variables, elderly patients with coronary artery disease have more severe lesions compared to younger patients and experience more frequent complications 16. Diabetes mellitus is considered to be the highest risk factor for cardiovascular morbidity and mortality17, leading to a three to five-fold higher chance of developing coronary artery disease18.

Likewise, the type of previous MR procedure is a marker of the severity of coronary artery disease. In patients undergoing previous PCI, the underlying coronary artery disease is often less marked. Those with previous MR often have left ventricular dysfunction or multivessel disease. Consequently, patients with PCI have a more favorable prognosis19.

Suspected ACS, with marked symmetric inversion of T-waves on the precordial leads, suggests acute ischemia, particularly due to critical nature of stenosis of the anterior descending coronary artery20.

Additionally, lesions involving a larger number of vessels are present in patients with positive troponin tests compared to those with negative troponin tests21.

It is believed that estimating the possible severity of coronary lesions before performing coronary angiography may contribute to more satisfactory therapeutic decisions22. For instance, in those with a high probability of having coronary lesions likely to require MR surgery, one may choose not to administer thienopyridines before performing cinecoronariography.

Garcia et al22 evaluated the correlation between TIMI risk score and the severity of coronary artery disease in 688 patients with non-ST elevation ACS undergoing coronary angiography (cine coronary arteriography). They excluded patients who had previous MR surgery or recent PCI. The authors concluded that for every increase in the risk category, there is an increase not only in the percentage of adverse events, but also the likelihood that patients will have disease involving three vessels or injury to the left main coronary artery. Unlike our work, the data from this study were limited by the retrospective analysis, which evaluated only the TIMI risk score.

Likewise, to explore the physiopathological basis of TIMI risk score variables, Mega et al23 analyzed the relationship between this model of risk stratification and coronary anatomy in 1,491 patients diagnosed with non-ST elevation ACS, who were included in the clinical trial PRISM-PLUS24. Patients with risk scores 5 - 7 (high risk) frequently presented with serious stenosis and multiarterial disease, compared to those with risk scores of 0 to 2 (low risk). Likelihood of injury in the left main coronary artery, presence of intracoronary thrombus and reduced flow in the culprit artery were progressively higher with increasing risk scores. Previous history of coronary artery disease, advanced age, and ST-segment deviation were variables of the TIMI risk score that showed the most significant association with the severity of coronary artery lesions. Moreover, elevated biomarkers of myocardial necrosis, ST-segment deviation and previous use of aspirin were significantly correlated with intracoronary thrombus and/or reduction of the blood flow in the culprit coronary artery. The data from this study partly explain the particular benefit of antithrombotics in patients at highest risk.

Recently, Ben Salem et al25 evaluated the extent and severity of coronary artery lesions in a retrospective analysis of 239 patients with non-ST elevation ACS. The authors classified patients into TIMI risk scores of low, intermediate and high risk and compared the angiographic findings among the three groups. It was observed that patients with risk scores of 0-2 had significantly more normal coronary angiography or insignificant coronary artery disease, compared with a score of 5-7 (36.3% versus 13%, p < 0.001). On the other hand, disease involving three vessels or lesions of the left main coronary artery were found more frequently among the high risk patients. The authors concluded that higher TIMI risk scores correlated with more severe arterial disease.

In our study we evaluated a population of 582 patients with non-ST elevation ACS, with characteristics very representative of the real world. Aiming to analyze the correlation between the risk scores currently recommended by the guidelines and the presence of more severe coronary artery lesions, this is the first study that assessed three risk stratification models simultaneously in the same population.

In the three risk scores analyzed, the mean score was significantly higher in patients with more severe coronary artery lesions, thereby validating the ability of the models to discriminate those with more important coronary artery disease. With this result, we decided to perform a multiple logistic regression analysis to assess the independent ability of each risk score to predict the presence or absence of coronary lesions > 50%.

In calculating the C statistic (area under the ROC curve) it can be seen that the TIMI risk score shows the best performance. This was demonstrated by comparing the areas under the ROC curve of the three models. The TIMI risk score showed the greatest ability to discriminate those likely to have a coronary lesion > 50%, predicting more accurately than the GRACE scores. The hospital GRACE score, in turn, was more accurate than the GRACE risk score in six months.

Limitations

This study has limitations. The results apply only to patients with non-ST elevation ACS who were referred for angiography and cannot be applied, therefore, to all patients with ACS. The study population was from a single center, and it is possible that the results could be applied to the real world of other centers.

Conclusion

The TIMI, hospital GRACE score and GRACE risk score in six months correlate with the severity of coronary lesions found by coronary angiography. The TIMI risk score showed better predictive ability to discriminate who is most likely to have a coronary lesion > 50%.

References

1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Heart disease and stroke statistics - 2010 update: a report from the American Heart Association. Circulation. 2010;121(7):e46-e215. Erratum in: Circulation. 2010 Mar 30;121(12):e260. Stafford, Randall [corrected to Roger, Véronique L]. Circulation. 2011 Oct 18;124(16):e425.

2. Nicolau JC, Timerman A, Piegas LS, Marin-Neto JA, Rassi A Jr. [Guidelines for Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction of the Brazilian Society of Cardiology (II Edition, 2007)]. Arq Bras Cardiol. 2007;89(4):e89-131.

3. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey Jr DE, et al. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007;116(7):e148-304.

4. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-42.

5. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163(19):2345-53.

6. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA. 2004;291(22):2727-33.

7. Siegel S, Castellan NJ. Nonparametric statistics. 2nd ed. New York: McGraw-Hill; 1988.

8. Fletcher RH, Fletcher SW, Wagner EH. Epidemiologia clínica - bases científicas da conduta médica. 2ª ed. Porto Alegre: Artes Médicas; 2009.

9. Hanley JA, McNeil BI. A method of comparing the areas under receive operating characteristic curves derived from the same cases. Radiology. 1983;148(3):839-43.

10. Braunwald E. Unstable angina: an etiologic approach to management. Circulation. 1998;98(21):2219-22.

11. Farhi JI, Cohen M, Fuster V. The broad spectrum of unstable angina pectoris and its implications for future controlled trials. Am J Cardiol. 1986;58(6):547-50.

12. Braunwald E, Mark DB, Jones RH, Brown J, Brown L, Cheitlin MD, et al. Unstable angina: diagnosis and management. Rockville (MD): Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, Public Health Service, US Department of Health and Human Services; 1994. (Clinical Practice Guideline, nº 10).

13. Calvin JE, Klein LW, VandenBerg BJ, Meyer P, Condon JV, Snell RJ, et al. Risk stratification in unstable angina: prospective validation of the Braunwald classification. JAMA. 1995;273(2):136-41.

14. Armstrong PW, Fu Y, Chang WC, Topol EJ, Granger CB, Betriu A, et al. Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia. The GUSTO-IIb Investigators. Circulation. 1998;98(18):1860-8.

15. Zaacks SM, Liebson PR, Calvin JE, Parrillo JE, Klein LW. Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J Am Coll Cardiol. 1999;33(1):107-18.

16. Stone PH, Thompson B, Anderson HV, Kronenberg MW, Gibson RS, Rogers WJ, et al. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry. JAMA. 1996;275(14):1104-12.

17. Stone PH, Thompson B, Anderson HV, Kronenberg MW, Gibson RS, Rogers WJ, et al. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry. JAMA. 1996;275(14):1104-12.

18. Roffi M, Chew DP, Mukherjee D, Bhatt DL, White JA, Heeschen C, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation. 2001;104(23):2767-71.

19. Bierman EL. George Lyman Duff Memorial Lecture. Atherogenesis in diabetes. Arterioscler Thromb. 1992;12(6):647-56.

20. Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation. 2000;101(22):2557-67.

21. de Zwaan C, Bär FW, Janssen JH, Cheriex EC, Dassen WR, Brugada P, et al. Angiographic and clinical characteristics of patients with unstable angina showing an ECG pattern indicating critical narrowing of the proximal LAD coronary artery. Am Heart J. 1989;117(3):657-65.

22. Newby LK, Kaplan AL, Granger BB, Sedor F, Califf RM, Ohman EM. Comparison of cardiac troponin T versus creatine kinase-MB for risk stratification in a chest pain evaluation unit. Am J Cardiol. 2000;85(7):801-5.

23. Garcia S, Canoniero M, Peter A, de Marchena E, Ferreira A. Correlation of TIMI risk score with angiographic severity and extent of coronary artery disease in patients with non-ST-elevation acute coronary syndromes. Am J Cardiol. 2004;93(7):813-6.

24. Mega JL, Morrow DA, Sabatine MS, Zhao XQ, Snapinn SM, DiBattiste PM, et al. Correlation between the TIMI risk score and high-risk angiographic findings in non-ST-elevation acute coronary syndromes: observations from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial. Am Heart J. 2005;149(5):846-50.

25. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med. 1998;338:1488-97. Erratum in N Engl J Med 1998 Aug 6;339(6):415.

26. Ben Salem H, Ouali S, Hammas S, Bougmiza I, Gribaa R, Ghannem K, et al. [Correlation of TIMI risk score with angiographic extent and severity of coronary artery disease in non-ST-elevation acute coronary syndromes]. Ann Cardiol Angeiol (Paris). 2011;60(2):87-91.