abcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCSão Paulo, SP, BrazilXvGP4BDPQMDdjkqVzHCZ4FrS0066-782X2012001300008S0066-782X(12)0990040810.1590/S0066-782X2012005000081Artigos OriginaisÍndice Internacional de Função Erétil Simplificado e doença coronariana em pacientes hipertensosCordeiroAntonio CarlosMizzaciCarolina ChristianiniFernandesRafael ModestoAraujo-JuniorAfrânio GaldinoCardosoPaulo OliveiraDutraLucas VellosoSousaAmanda Guerra Moraes RegoAmodeoCelsoSão PauloSão PauloInstituto Dante Pazzanese de CardiologiaBrazil102012994924930110120121805201213012012This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
FUNDAMENTO: A Disfunção Erétil (DE) se associa ao risco aumentado de Doença Arterial Coronariana (DAC). OBJETIVO: Avaliar a associação entre DE, determinada pelo Índice Internacional de Função Erétil Simplificado (IIFE-5), e DAC. MÉTODOS: Estudo de corte transversal que avaliou 263 hipertensos (55 [50 - 61] anos). A DE foi avaliada pelo IIEF-5 e a DAC, por meio da história de revascularização miocárdica prévia e/ou por cineangiocoronariografia. RESULTADOS: O IIFE-5 se correlacionou com o clearance de creatinina [ClCr] (Rho = 0,23; p < 0,001) e com a idade (Rho = -0,22; p < 0,001). Quarenta e dois pacientes apresentavam DAC; e o IIFE-5 foi capaz de discriminá-los (área sob a curva ROC = 0,63; p = 0,006). Os pacientes foram divididos em dois grupos: IIFE-5 < 20 (n = 140) e IIFE- 5 > 20 (n = 123); aqueles com menor IIFE-5 tinham idade mais elevada (57 [52 - 61] vs. 54 [45 - 60] anos; p = 0,002), maior prevalência de DAC (22% vs. 9%; p = 0,004), tabagismo (64% vs. 47%; p = 0,009) e do uso de inibidores dos canais de cálcio (65 % vs. 43%; p = 0,001), além de menor ClCr (67,3 [30,8 - 88,6] vs. 82,6 [65,9 - 98,2] ml/min; p < 0,001). O IIFE-5 < 20 se associou ao maior risco de DAC em regressão logística; tanto univariada (RR = 2,89 [IC 95% 1,39 - 6,05]), quanto após ajustes para idade, diabetes, ClCr, tabagismo, pressão arterial média e uso de anti- hipertensivos (RR = 2,59 [IC 95%: 1,01 - 6,61]). CONCLUSÃO: O IIFE-5 se associa ao diagnóstico de DAC e sua utilização pode agregar informação ao estadiamento do risco cardiovascular em pacientes hipertensos.
Disfunção erétilhipertensãodoença da artéria coronariana04092012
Índice Internacional de Função Erétil Simplificado e doença coronariana em pacientes hipertensos
Antonio Carlos Cordeiro; Carolina Christianini Mizzaci; Rafael Modesto Fernandes; Afrânio Galdino Araujo-Junior; Paulo Oliveira Cardoso; Lucas Velloso Dutra; Amanda Guerra Moraes Rego Sousa; Celso Amodeo
Instituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brasil
Correspondência
RESUMO
FUNDAMENTO: A Disfunção Erétil (DE) se associa ao risco aumentado de Doença Arterial Coronariana (DAC).
OBJETIVO: Avaliar a associação entre DE, determinada pelo Índice Internacional de Função Erétil Simplificado (IIFE-5), e DAC.
MÉTODOS: Estudo de corte transversal que avaliou 263 hipertensos (55 [50 - 61] anos). A DE foi avaliada pelo IIEF-5 e a DAC, por meio da história de revascularização miocárdica prévia e/ou por cineangiocoronariografia.
RESULTADOS: O IIFE-5 se correlacionou com o clearance de creatinina [ClCr] (Rho = 0,23; p < 0,001) e com a idade (Rho = -0,22; p < 0,001). Quarenta e dois pacientes apresentavam DAC; e o IIFE-5 foi capaz de discriminá-los (área sob a curva ROC = 0,63; p = 0,006). Os pacientes foram divididos em dois grupos: IIFE-5 < 20 (n = 140) e IIFE- 5 > 20 (n = 123); aqueles com menor IIFE-5 tinham idade mais elevada (57 [52 - 61] vs. 54 [45 - 60] anos; p = 0,002), maior prevalência de DAC (22% vs. 9%; p = 0,004), tabagismo (64% vs. 47%; p = 0,009) e do uso de inibidores dos canais de cálcio (65 % vs. 43%; p = 0,001), além de menor ClCr (67,3 [30,8 - 88,6] vs. 82,6 [65,9 - 98,2] ml/min; p < 0,001). O IIFE-5 < 20 se associou ao maior risco de DAC em regressão logística; tanto univariada (RR = 2,89 [IC 95% 1,39 - 6,05]), quanto após ajustes para idade, diabetes, ClCr, tabagismo, pressão arterial média e uso de anti- hipertensivos (RR = 2,59 [IC 95%: 1,01 - 6,61]).
CONCLUSÃO: O IIFE-5 se associa ao diagnóstico de DAC e sua utilização pode agregar informação ao estadiamento do risco cardiovascular em pacientes hipertensos.
Palavras-chave: Disfunção erétil; hipertensão; doença da artéria coronariana.
Introdução
A Disfunção Erétil (DE), incapacidade de obter e manter ereção peniana suficiente para uma relação sexual satisfatória1, afeta aproximadamente 150 milhões de homens em todo o mundo2; e se associa à maior prevalência de fatores de risco cardiovascular como Diabetes Mellitus (DM)3, Hipertensão Arterial Sistêmica (HAS), dislipidemia, obesidade, tabagismo e síndrome metabólica4-6. No Brasil, Moreira e cols.7, em estudo multicêntrico que envolveu 1.286 homens a partir dos 18 anos, descreveram a presença de algum grau de DE em 46% dos participantes.
A aterosclerose é uma das principais causas de DE, de tal forma que indivíduos que desenvolvem disfunção erétil têm risco aumentado para o desenvolvimento de outras manifestações da doença aterosclerótica como Acidente Vascular Encefálico (AVE) e Doença Arterial Coronariana (DAC)8-13, mesmo após o ajuste para fatores tradicionalmente relacionados à doença cardiovascular14. Além disso, existem evidências de que o grau de DE se associa à gravidade da DAC15.
A presença e a gravidade da DE podem ser analisadas por meio do Índice Internacional de Função Erétil (IIFE), questionário autoaplicável, composto de 15 itens que abrangem diferentes áreas relacionadas à função sexual (ereção, orgasmo, desejo e satisfação)16. Rosen e cols.17 desenvolveram uma versão simplificada desse questionário, composta por apenas cinco itens (IIEF-5), que tem se mostrado uma ferramenta prática para diagnóstico e classificação da DE. Nosso objetivo foi avaliar a associação entre a presença de disfunção erétil, avaliada pelo IIEF-5, e o diagnóstico de DAC em pacientes hipertensos.
Métodos
Pacientes e metodologia
Realizamos um estudo de corte transversal que avaliou todos os pacientes do sexo masculino, com idade entre 18 e 65 anos, consecutivamente atendidos na Seção de Hipertensão e Nefrologia do Instituto Dante Pazzanese de Cardiologia (IDPC) entre 3 de abril e 31 de maio de 2010 e que manifestaram interesse em participar do estudo, manifestado mediante assinatura do Termo de Consentimento Livre e Esclarecido. O intervalo de idade para inclusão representa aquele necessário para o encaminhamento de pacientes à Seção de Hipertensão e Nefrologia do IDPC. O estudo foi aprovado pelo Comitê de Ética em pesquisa do IDPC.
Após consulta clinicocardiológica detalhada, os pacientes foram instados a responder o questionário autoaplicável do Índice Internacional de Função Erétil (IIEF-5)17. Por meio do questionário IIEF-5, foi determinada a presença e a gravidade da DE: ausência (>21), leve (17-21), leve/moderada (12-16), moderada (8-11) e severa (<8).
Todos os pacientes tiveram peso e altura mensurados no momento da consulta. Os exames laboratoriais (glicemia, creatinina, colesterol total e triglicerídeos), realizados no Laboratório do IDPC e trazidos para a consulta médica, foram considerados na análise. O ritmo de filtração glomerular foi calculado pela equação de Cockroft-Gault18, com ajuste para a superfície corporal. A Pressão Arterial Média (PAM), calculada pela fórmula "(pressão arterial sistólica +[2* pressão arterial diastólica])/3" por melhor representar a pressão de perfusão tecidual, foi utilizada para as análises. O diagnóstico de DAC foi realizado por meio de revisão do prontuário, com base na história de revascularização miocárdica (cirúrgica/percutânea) prévia ou na presença de lesão coronariana > 50% através de cineangiocoronariografia.
Análise estatística
A análise da distribuição dos dados foi realizada pelo teste de Kolmogorov-Smirnov. Utilizamos a análise Receiver-Operating Characteristic (ROC) para estabelecer o valor do IIEF-5 que melhor identificasse a presença de DAC. As variáveis contínuas, quando paramétricas, foram representadas por média e desvio padrão; e quando de distribuição não normal, por mediana e percentis (25 - 75). Para a análise de correlação entre as variáveis contínuas, foi utilizado o teste de correlação de Spearman (Rho); e quando da comparação de valores entre dois grupos distintos, foi utilizado o teste de Mann-Whitney. Variáveis categóricas foram representadas por valor absoluto (n) e relativo (%) e para comparações de proporções entre dois grupos independentes foi utilizado o teste Qui-quadrado de Pearson. Realizamos análise de regressão logística para avaliar os fatores associados à presença de disfunção erétil.
Com base em dados de literatura, onde a proporção de disfunção erétil foi de 47% em pacientes com DAC e 24% em controles19, o tamanho de amostra mínimo necessário para que nossos resultados apresentassem um nível de significância 5% e poder de teste de 90% foi calculado em 178 pacientes (89 por grupo). Todas as probabilidades de significância (valores de p) apresentadas são do tipo bicaudal e valores menores que 0,05 foram considerados estatisticamente significativos. A análise estatística foi realizada com o software SPSS 13.0 (SPSS Inc., Chicago IL, 2004).
Resultados
Foram avaliados 263 pacientes, com mediana da idade 55 (50 - 61) anos, cujos dados clínicos e demográficos são descritos na Tabela 1. Cento e cinquenta e cinco pacientes (59%) apresentaram algum grau de disfunção erétil de acordo com o questionário IIEF-5 (Tabela 1 e Figura 1).
O questionário IIEF-5 se correlacionou negativamente com a idade (rho = - 0,22; p < 0,001) e positivamente com o clearance de creatinina (rho = 0,23; p < 0,001), como apresentado na Tabela 2. Pacientes com antecedentes de DAC apresentavam menor IIEF-5 (17 [8-21] vs. 21 [15 - 23]; p = 0,006), Figura 2. O questionário IIEF-5 foi capaz de discriminar indivíduos com diagnóstico de DAC (área sobre a curva ROC = 0,63; p = 0,006), como pode ser observado na Figura 3; sendo "20" a pontuação do IIEF-5 mais apropriada para este objetivo.
Os pacientes foram divididos em dois grupos de acordo com o IIEF-5 (< 20 e > 20) e suas características clínico-demográficas são descritas na Tabela 3. Em resumo, pacientes com menor IIEF-5 tinham idade mais elevada (57 anos [52 - 61] vs. 54 anos [45 - 60]; p = 0,002), maior prevalência de DAC (22% vs. 9%; p = 0,004), maior histórico de tabagismo (64% vs. 47%; p = 0,009) e maior prevalência do uso de inibidores dos canais de cálcio (65 % vs. 43%; p = 0,001), além de menor clearance de creatinina (67,3 mL/min [30,8 - 88,6] vs. 82,6 mL/min [65,9 - 98,2]; p < 0,001).
A análise de regressão logística (Tabela 4) evidenciou que o IIEF-5 < 20 se associava à presença de DAC tanto na análise univariada (Risco relativo = 2,89 [IC 95% 1,39 -6,05]) quanto após ajustes para potenciais fatores de confusão, como idade, diabetes mellitus, doença renal, tabagismo, pressão arterial média, uso de inibidores da enzima de conversão da angiotensina/bloqueadores do receptor AT1 da angiotensina II, diuréticos, bloqueadores dos canais de cálcio e betabloqueadores e (Risco Relativo = 2,59 [IC 95%: 1,01 - 6,61]).
Discussão
O presente estudo mostrou que pacientes hipertensos com IIEF-5 < 20 têm risco 2,59 vezes maior de apresentar diagnóstico de DAC de forma independente da presença de reconhecidos fatores de risco cardiovascular (idade, diabetes, doença renal e tabagismo) e do uso de anti-hipertensivos, reconhecidamente associados ao desenvolvimento de disfunção erétil. Nossos resultados reforçam as evidências da associação entre DE e DAC9,11,20-22.
A DE é considerada uma manifestação clínica de alterações vasculares, funcionais e estruturais, decorrentes da doença cardiovascular generalizada; sendo a circulação peniana afetada de forma mais precoce em virtude do menor diâmetro das artérias penianas, quando comparadas às coronárias, carótidas e femorais11. Dessa forma, DE e DAC podem ser consideradas diferentes manifestações da mesma doença, o que é realçado pelo fato de os fatores de riscos associados à DAC serem comumente encontrados em pacientes com DE23, bem como o grau da DE se relacionar à gravidade da DAC24. De fato, evidenciamos que pacientes com DAC, quando comparados àqueles sem antecedentes de coronariopatias, tinham o IIEF-5 significativamente menor.
A estratificação do risco cardiovascular é etapa essencial para o estabelecimento das metas pressóricas a serem alcançadas em pacientes hipertensos25. Dessa forma, sabendo-se que a prevalência de DE é extremamente elevada em pacientes com DAC19,20, sendo aquela um preditor independente de risco para o desenvolvimento desta, além de precedê-la, em média, por três anos20, seria razoável a realização do "screening" para DE em todos os pacientes com fatores de risco para o desenvolvimento de doença cardiovascular. Contudo, por se tratar de uma condição necessariamente autorreportada, muitas vezes propositalmente omitida e sem testes confirmatórios específicos à disposição, a pesquisa de disfunção erétil em consultórios de cardiologia é geralmente negligenciada. Nesse sentido, nossos resultados, evidenciando a associação independente entre o questionário IIEF-5 - ferramenta diagnóstica simples e de fácil aplicabilidade para o diagnóstico da presença e gravidade da DE17 - e a presença de DAC, ressaltam a sua utilidade no dia a dia dos consultórios, quando pode ser aplicado ainda nas salas de espera, tanto para a identificação da disfunção erétil quanto para estratificação do risco cardiovascular.
Em nossos pacientes, a prevalência de disfunção erétil (59%) foi superior à descrita em outros estudos com a população brasileira7,22,27,28, o que pode ser atribuído ao fato de nossa amostra incluir apenas pacientes hipertensos29,30. Ressaltamos ainda que o "cut-off" de 20 para o IIEF-5 adotado em nossa análise inclui pacientes com DE leve de acordo com a classificação original17; o que pode estar relacionado a falhas na classificação ou à maior prevalência de alterações psíquicas e não orgânicas como causa de DE em pacientes com IIEF-5 limítrofe. Nosso estudo tem limitações, dentre as quais: a) o fato de se tratar de estudo de corte transversal, que apenas permite o estabelecimento de associações; b) o pequeno número de pacientes avaliados; c) a falta de informação quanto à dose utilizada de anti-hipertensivos; e d) o fato de o diagnóstico de DAC ter sido baseado apenas na história clínica e revisão de prontuário. Contudo, o diagnóstico de DAC é inicialmente aventado com base na anamnese do paciente; nesse sentido, nosso estudo simulou as condições encontradas pelo clínico em sua rotina diária.
Conclusão
A presença de disfunção erétil está associada ao risco aumentado de doença arterial coronariana. A utilização do IIFE-5 na consulta médica de rotina pode agregar informação ao estadiamento do risco cardiovascular em pacientes de consultório.
Potencial Conflito de Interesses
Declaro não haver conflito de interesses pertinentes.
Fontes de Financiamento
O presente estudo não teve fontes de financiamento externas.
Vinculação Acadêmica
Este artigo é parte do Trabalho de Conclusão de Curso de Residência Médica em Cardiologia dos alunos, Carolina Christianini Mizzaci, Rafael Modesto Fernandes, Afrânio Galdino de Araújo Junior, Paulo Oliveira Cardoso, Lucas Velloso Dutra pelo Instituto Dante Pazzanese de Cardiologia - São Paulo, SP.
Antonio Carlos Cordeiro
Instituto Dante Pazzanese de Cardiologia, Seção de Hipertensão e Nefrologia
Avenida Dr. Dante Pazzanese 500, Vila Mariana
CEP 04012-909, São Paulo, SP - Brasil
E-mail:
antonio.cordeiro@cardiol.br,
accordeirojr@uol.com.br
Artigo recebido em 11/01/12; revisado em 13/01/12; aceito em 18/05/12.
1. Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol. 2010;57(5):804-14.Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculationEur Urol201080414557HatzimouratidisKAmarEEardleyIGiulianoFHatzichristouDMontorsiF2. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84(1):50-6.The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequencesBJU Int1999506184AytaIAMcKinlayJBKraneRJ3. Burke JP, Jacobson DJ, McGree ME, Nehra A, Roberts RO, Girman CJ, et al. Diabetes and sexual dysfunction: results from the Olmsted County study of urinary symptoms and health status among men. J Urol. 2007;177(4):1438-42.Diabetes and sexual dysfunction: results from the Olmsted County study of urinary symptoms and health status among menJ Urol20071438424177BurkeJPJacobsonDJMcGreeMENehraARobertsROGirmanCJ4. Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med. 2003;139(3):161-8.Sexual function in men older than 50 years of age: results from the health professionals follow-up studyAnn Intern Med200316183139BaconCGMittlemanMAKawachiIGiovannucciEGlasserDBRimmEB5. Bal K, Oder M, Sahin AS, Karatas CT, Demir O, Can E, et al. Prevalence of metabolic syndrome and its association with erectile dysfunction among urologic patients: metabolic backgrounds of erectile dysfunction. Urology. 2007;69(2):356-60.Prevalence of metabolic syndrome and its association with erectile dysfunction among urologic patients: metabolic backgrounds of erectile dysfunctionUrology200735660269BalKOderMSahinASKaratasCTDemirOCanE6. Saigal CS, Wessells H, Pace J, Schonlau M, Wilt TJ; Urologic Diseases in America Project. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166(2):207-12.Predictors and prevalence of erectile dysfunction in a racially diverse populationArch Intern Med2006207122166SaigalCSWessellsHPaceJSchonlauMWiltTJ7. Moreira ED Jr, Abdo CH, Torres EB, Lobo CF, Fittipaldi JA. Prevalence and correlates of erectile dysfunction: results of the Brazilian study of sexual behavior. Urology. 2001;58(4):583-8.Prevalence and correlates of erectile dysfunction: results of the Brazilian study of sexual behaviorUrology20015838458Moreira JrEDAbdoCHTorresEBLoboCFFittipaldiJA8. Bolona ER, Uraga MV, Haddad RM, Tracz MJ, Sideras K, Kennedy CC, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82(1):20-8.Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trialsMayo Clin Proc2007208182BolonaERUragaMVHaddadRMTraczMJSiderasKKennedyCC9. Elesber AA, Solomon H, Lennon RJ, Mathew V, Prasad A, Pumper G, et al. Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis. Eur Heart J. 2006;27(7):824-31.Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosisEur Heart J200682431727ElesberAASolomonHLennonRJMathewVPrasadAPumperG10. Montorsi P, Ravagnani PM, Galli S, Rotatori F, Briganti A, Salonia A, et al. The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Am J Cardiol. 2005;96(12B):19M-23M.The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery diseaseAm J Cardiol200519M23M12B96MontorsiPRavagnaniPMGalliSRotatoriFBrigantiASaloniaA11. Ponholzer A, Temml C, Obermayr R, Wehrberger C, Madersbacher S. Is erectile dysfunction an indicator for increased risk of coronary heart disease and stroke? Eur Urol. 2005;48(3):512-8.Is erectile dysfunction an indicator for increased risk of coronary heart disease and stroke?Eur Urol20055128348PonholzerATemmlCObermayrRWehrbergerCMadersbacherS12. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005;294(23):2996-3002.Erectile dysfunction and subsequent cardiovascular diseaseJAMA20052996300223294ThompsonIMTangenCMGoodmanPJProbstfieldJLMoinpourCMColtmanCA13. Vlachopoulos C, Aznaouridis K, Ioakeimidis N, Rokkas K, Vasiliadou C, Alexopoulos N, et al. Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease. Eur Heart J. 2006;27(22):2640-8.Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery diseaseEur Heart J2006264082227VlachopoulosCAznaouridisKIoakeimidisNRokkasKVasiliadouCAlexopoulosN14. Araujo AB, Hall SA, Ganz P, Chiu GR, Rosen RC, Kupelian V, et al. Does erectile dysfunction contribute to cardiovascular disease risk prediction beyond the Framingham risk score? J Am Coll Cardiol. 2010;55(4):350-6.Does erectile dysfunction contribute to cardiovascular disease risk prediction beyond the Framingham risk score?J Am Coll Cardiol20103506455AraujoABHallSAGanzPChiuGRRosenRCKupelianV15. Le NA. Inflammation, oxidative stress, and atherosclerosis. Curr Opin Lipidol. 2004;15(2):227-9.Inflammation, oxidative stress, and atherosclerosisCurr Opin Lipidol20042279215LeNA16. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49(6):822-30.The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunctionUrology199782230649RosenRCRileyAWagnerGOsterlohIHKirkpatrickJMishraA17. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999;11(6):319-26.Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunctionInt J Impot Res199931926611RosenRCCappelleriJCSmithMDLipskyJPenaBM18. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.Prediction of creatinine clearance from serum creatinineNephron19763141116CockcroftDWGaultMH19. Montorsi P, Ravagnani PM, Galli S, Rotatori F, Veglia F, Briganti A, et al. Association between erectile dysfunction and coronary artery disease: role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial. Eur Heart J. 2006;27(22):2632-9.Association between erectile dysfunction and coronary artery disease: role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trialEur Heart J2006263292227MontorsiPRavagnaniPMGalliSRotatoriFVegliaFBrigantiA20. Montorsi F, Briganti A, Salonia A, Rigatti P, Margonato A, Macchi A, et al. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur Urol. 2003;44(3):360-4.Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery diseaseEur Urol20033604344MontorsiFBrigantiASaloniaARigattiPMargonatoAMacchiA21. Dong JY, Zhang YH, Qin LQ. Erectile dysfunction and risk of cardiovascular disease meta-analysis of prospective cohort studies. J Am Coll Cardiol. 2011;58(13):1378-85.Erectile dysfunction and risk of cardiovascular disease meta-analysis of prospective cohort studiesJ Am Coll Cardiol20111378851358DongJYZhangYHQinLQ22. Ortiz J, Ortiz ST, Monaco CG, Yamashita CH, Moreira MC, Monaco CA. [Erectile dysfunction: a marker for myocardial perfusion impairment?]. Arq Bras Cardiol. 2005;85(4):241-6.Erectile dysfunction: a marker for myocardial perfusion impairment?Arq Bras Cardiol20052416485OrtizJOrtizSTMonacoCGYamashitaCHMoreiraMCMonacoCA23. Sullivan ME, Keoghane SR, Miller MA. Vascular risk factors and erectile dysfunction. BJU Int. 2001;87(9):838-45.Vascular risk factors and erectile dysfunctionBJU Int200183845987SullivanMEKeoghaneSRMillerMA24. Salem S, Abdi S, Mehrsai A, Saboury B, Saraji A, Shokohideh V, et al. Erectile dysfunction severity as a risk predictor for coronary artery disease. J Sex Med. 2009;6(12):3425-32.Erectile dysfunction severity as a risk predictor for coronary artery diseaseJ Sex Med2009342532126SalemSAbdiSMehrsaiASabouryBSarajiAShokohidehV25. Sociedade Brasileira de Cardiologia, Sociedade Brasileira de Hipertensão, Sociedade Brasileira de Nefrologia. VI Diretrizes brasileiras de hipertensão. Arq Bras Cardiol. 2010;95(1 supl.1):1-51.VI Diretrizes brasileiras de hipertensãoArq Bras Cardiol201015119526. Rhoden EL, Teloken C, Sogari PR, Vargas Souto CA. The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. Int J Impot Res. 2002;14(4):245-50.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunctionInt J Impot Res200224550414RhodenELTelokenCSogariPRVargas SoutoCA27. Moreira ED Jr, Bestane WJ, Bartolo EB, Fittipaldi JA. Prevalence and determinants of erectile dysfunction in Santos, southeastern Brazil. Sao Paulo Med J. 2002;120(2):49-54.Prevalence and determinants of erectile dysfunction in Santos, southeastern BrazilSao Paulo Med J200249542120Moreira JrEDBestaneWJBartoloEBFittipaldiJA28. Reis MM, Abdo CH. Prevalence of erectile dysfunction as defined by the International Index of Erectile Function (IIEF) and self-reported erectile dysfunction in a sample of Brazilian men who consider themselves healthy. J Sex Marital Ther. 2010;36(1):87-100.Prevalence of erectile dysfunction as defined by the International Index of Erectile Function (IIEF) and self-reported erectile dysfunction in a sample of Brazilian men who consider themselves healthyJ Sex Marital Ther201087100136ReisMMAbdoCH29. Doumas M, Douma S. Sexual dysfunction in essential hypertension: myth or reality? J Clin Hypertens (Greenwich). 2006;8(4):269-74.Sexual dysfunction in essential hypertension: myth or reality?J Clin Hypertens20062697448DoumasMDoumaS30. Fogari R, Zoppi A. Effects of antihypertensive therapy on sexual activity in hypertensive men. Curr Hypertens Rep. 2002;4(3):202-10.Effects of antihypertensive therapy on sexual activity in hypertensive menCurr Hypertens Rep20022021034FogariRZoppiAOriginal ArticlesSimplified International Index of Erectile Function (IIEF-5) and coronary artery disease in hypertensive patients
BACKGROUND: Erectile Dysfunction (ED) is associated with increased risk of coronary artery disease (CAD). OBJECTIVE: To evaluate the association between ED, determined by the Simplified International Index of Erectile Function (IIEF-5) and CAD. METHODS: This was a cross-sectional cohort study that evaluated 263 hypertensive patients (55 [50-61] years). ED was assessed through the IIEF-5 and CAD by the history of previous myocardial revascularization and/or coronary angiography. RESULTS: The IIEF-5 correlated with creatinine clearance [CrCl] (Rho = 0.23, p <0.001) and age (Rho = -0.22, p <0.001). Forty-two patients had CAD, and IIEF-5 was able to discriminate them (area under the ROC curve = 0.63, p = 0.006). Patients were divided into two groups: IIEF-5 < 20 (n = 140) and IIEF-5 > 20 (n = 123); those with lower IIEF-5 scores were older (57 [52-61] vs. 54 [45-60] years, p = 0.002), had higher prevalence of CAD (22% vs. 9%, p = 0.004), smoking (64% vs. 47%, p = 0.009) and use of calcium channel inhibitors (65% vs. 43.%, p = 0.001), as well as lower CrCl (67.3 [30.8 to 88.6] vs. 82.6 [65.9 - 98.2] ml/min, p <0.001). The IIEF-5 < 21 was associated with increased risk of CAD in the logistic regression, both univariate (RR = 2.89 [95%CI: 1.39 - 6.05]), and after adjusting for age, diabetes, CrCl, smoking, mean arterial pressure and use of antihypertensive drugs (RR = 2.59 [95% CI: 1.01 - 6.61]). CONCLUSION: The IIEF-5 is associated with the diagnosis of CAD and its use can add information to cardiovascular risk staging in hypertensive patients.
Antonio Carlos Cordeiro; Carolina Christianini Mizzaci; Rafael Modesto Fernandes; Afrânio Galdino Araujo-Junior; Paulo Oliveira Cardoso; Lucas Velloso Dutra; Amanda Guerra Moraes Rego Sousa; Celso Amodeo
Instituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brasil
Mailing Address
ABSTRACT
BACKGROUND: Erectile Dysfunction (ED) is associated with increased risk of coronary artery disease (CAD).
OBJECTIVE: To evaluate the association between ED, determined by the Simplified International Index of Erectile Function (IIEF-5) and CAD.
METHODS: This was a cross-sectional cohort study that evaluated 263 hypertensive patients (55 [50-61] years). ED was assessed through the IIEF-5 and CAD by the history of previous myocardial revascularization and/or coronary angiography.
RESULTS: The IIEF-5 correlated with creatinine clearance [CrCl] (Rho = 0.23, p <0.001) and age (Rho = -0.22, p <0.001). Forty-two patients had CAD, and IIEF-5 was able to discriminate them (area under the ROC curve = 0.63, p = 0.006). Patients were divided into two groups: IIEF-5 < 20 (n = 140) and IIEF-5 > 20 (n = 123); those with lower IIEF-5 scores were older (57 [52-61] vs. 54 [45-60] years, p = 0.002), had higher prevalence of CAD (22% vs. 9%, p = 0.004), smoking (64% vs. 47%, p = 0.009) and use of calcium channel inhibitors (65% vs. 43.%, p = 0.001), as well as lower CrCl (67.3 [30.8 to 88.6] vs. 82.6 [65.9 - 98.2] ml/min, p <0.001). The IIEF-5 < 21 was associated with increased risk of CAD in the logistic regression, both univariate (RR = 2.89 [95%CI: 1.39 - 6.05]), and after adjusting for age, diabetes, CrCl, smoking, mean arterial pressure and use of antihypertensive drugs (RR = 2.59 [95% CI: 1.01 - 6.61]).
CONCLUSION: The IIEF-5 is associated with the diagnosis of CAD and its use can add information to cardiovascular risk staging in hypertensive patients.
Erectile Dysfunction (ED), the incapacity to achieve and maintain a penile erection sufficient to have satisfactory sexual intercourse1 affects approximately 150 million men around the world2 and is associated with higher prevalence of cardiovascular risk factors, such as diabetes mellitus (DM)3, Systemic Arterial Hypertension (SAH), dyslipidemia, obesity, smoking and metabolic syndrome4-6. In Brazil, Moreira et al.7, in a multicenter study involving 1286 men aged 18 years and older, described the presence of some degree of ED in 46% of the participants.
Atherosclerosis is a major cause of ED, thus individuals who develop erectile dysfunction are at increased risk for developing other manifestations of atherosclerotic disease, such as Stroke and Coronary Artery Disease (CAD) 8-13, even after adjusting for factors traditionally related to cardiovascular disease14. Furthermore, there is evidence that the degree of ED is associated with CAD severity15.
The presence and severity of ED can be assessed using the International Index of Erectile Function (IIEF), a self-administered questionnaire consisting of 15 items, covering different areas related to sexual function (erection, orgasm, desire and satisfaction)16.
Rosen et al.17 developed a simplified version of the questionnaire, consisting of only five items (IIEF-5), which has been shown to be a practical tool for ED diagnosis and classification. Our objective was to evaluate the association between the presence of erectile dysfunction, as assessed by the IIEF-5, and the diagnosis of CAD in hypertensive patients.
Methods
Patients and methods
We performed a cross-sectional study that evaluated all men aged between 18 to 65 years, consecutively attended in the Section of Hypertension and Nephrology of Instituto Dante Pazzanese de Cardiologia (IDPC - outpatients clinic) between April 3 and May 31, 2010 and demonstrated interest in participating in the study by signing the informed consent form. The age range for inclusion is that necessary for the referral of patients to the Section of Hypertension and Nephrology IDPC outpatients clinic. The study was approved by the Ethics of Committee of IDPC.
After detailed clinical and cardiologic assessment, patients were asked to answer the self-administered questionnaire of the International Index of Erectile Function (IIEF-5)17. The IIEF-5 questionnaire score determined the presence and severity of ED: absent (> 21), mild (17-21), mild / moderate (12-16), moderate (8-11) and severe (<8)
All patients had weight and height measured at the time of consultation. Laboratory tests (glucose, creatinine, total cholesterol and triglycerides) performed at the Laboratory of IDPC and brought to the medical consultation, were considered in the analysis. Glomerular filtration rate was calculated by the Cockroft-Gault equation18, adjusted for body surface area. The mean arterial pressure (MAP), calculated by the formula "(systolic blood pressure + [2 * diastolic blood pressure]) / 3" was used in the analysis, as it is the best method of measuring tissue perfusion pressure. The CAD diagnosis was performed by reviewing medical records, based on the revascularization history (surgical/percutaneous) or presence of prior coronary lesion > 50% at the coronary angiography.
Statistical analysis
Data distribution analysis was performed using the Kolmogorov-Smirnov test. The analysis of the receiver-operating characteristic (ROC) was used to establish the value of IIEF-5 that best identified the presence of CAD. The variables were expressed as mean ± standard deviation, median (interquartile range, IQR) or as percentage, as appropriate. As many values were not normally distributed, Spearman's rank correlation (Rho) was used to determine correlations. Groups were compared by Mann-Whitney test or Chi-square analysis, as appropriate. Crude and adjusted logistic regression analyses were performed to evaluate the association between coronary artery disease and erectile dysfunction.
Based on literature data, where the proportion of erectile dysfunction was 47% in patients with CAD and 24% in controls19, the minimum sample size required for our results to have a significance level of 5% and test power of 90 % was calculated at 178 patients (89 per group). All probabilities of significance (p values) are two-tailed and values < 0.05 were considered statistically significant. Statistical analysis was performed using SPSS 13.0 software (SPSS Inc., Chicago IL, 2004).
Results
We evaluated 263 patients with median age of 55 (50-61) years, whose demographic and clinical data are described in Table 1. One hundred and fifty-five patients (59%) had some degree of erectile dysfunction according to IIEF-5 questionnaire (Table 1 and Figure 1).
The IIEF-5 questionnaire was negatively correlated with age (rho = - 0.22, p < 0.001) and positively correlated with creatinine clearance (rho = 0.23, p <0.001), as shown in Table 2. Patients with a history of CAD had lower IIEF-5 (17 [8-21] vs. 21. [15-23], p = 0.006), Figure 2. The IIEF-5 questionnaire was able to discriminate individuals with a diagnosis of CAD (area under ROC curve = 0.63, p = 0.006), as shown in Figure 3, and "20" was the IIEF-5 score considered to be more appropriate for this purpose.
The patients were divided into two groups according to the IIEF-5 score (< 20 and > 20) and their clinical and demographic characteristics are described in Table 3. In summary, patients with lower IIEF-5 were older (57 years [52-61] vs. 54 years [45-60], p = 0.002), had a higher prevalence of CAD (22% vs. 9%, p = 0.004), smoking (64% vs. 47%, p = 0.009) and use of calcium channel inhibitors (65% vs. 43.%, p = 0.001), as well as a lower creatinine clearance (67.3 mL / min [30.8 to 88.6] vs. 82.6 mL / min [65.9 to 98.2], p <0.001).
The logistic regression analysis (Table 4) showed that IIEF-5 score < 20 was associated with the presence of CAD in both the univariate analysis (odds ratio = 2.89 [95%CI: 1.39-6.05]) and even after adjustments for potential confounders such as age, diabetes mellitus, kidney disease, smoking, mean arterial pressure, use of angiotensin-converting enzyme inhibitors / angiotensin II receptor blockers, diuretics, calcium channel blockers and beta blockers (odds ratio = 2.59 [95%CI: 1.01 - 6.61]).
Discussion
The present study showed that hypertensive patients with IIEF-5 score < 20 have a 2.59-fold higher odds of presenting diagnosis of CAD, regardless of the presence of known cardiovascular risk factors (age, diabetes, kidney disease and smoking) and the use of antihypertensive drugs, known to be associated with the development of erectile dysfunction. Our results provide further evidence of the association between ED and CAD9,11,20-22.
ED is considered a clinical manifestation of vascular functional and structural alterations, resulting from widespread cardiovascular disease, with penile circulation being affected earlier due to the smaller diameter of the penile arteries, when compared to coronary, carotid and femoral arteries11. Thus, ED and CAD may be considered different manifestations of the same disease, which is highlighted by the fact that the risk factors associated with CAD are commonly found in patients with ED23, as well as by the correlation between ED degree and CAD severity24. In fact, we observed that patients with CAD, when compared to those with no history of coronary artery disease, had a significantly lower IIEF-5.
The stratification of cardiovascular risk is an essential step to establish BP goals to be achieved in hypertensive patients25. Thus, given that the prevalence of ED is extremely high in patients with CAD19,20, with the first being an independent risk predictor for the development of the latter, in addition to preceding it on average by three years20, it would be reasonable to perform ED screening in all patients with risk factors for cardiovascular disease development. However, as this is a self-reported condition, often purposely omitted and with no specific confirmatory tests available, the investigation of erectile dysfunction by cardiologists is usually neglected.
In this set, our results, by showing the independent association between the IIEF-5 questionnaire - a simple and easy-to-use tool to diagnose the presence and severity of ED17 - and the presence of CAD, highlight their usefulness in everyday routine of medical offices, where it can be applied even in waiting rooms, both for the identification of erectile dysfunction and also for cardiovascular risk stratification.
The prevalence of erectile dysfunction in our patients (59%) was higher than that described in other studies with the Brazilian population7,22,27,28, which may be attributed to the fact that our sample included only hypertensive patients29,30. We also emphasize that the cutoff of 20 for the IIEF-5 adopted in our analysis includes patients with mild ED according to the original classification17, which may be related to failure in the classification or higher prevalence of psychiatric and non-organic alterations as cause of ED in patients with borderline IIEF-5 score. Our study has limitations, including: a) its cross-sectional design, which only allows the establishment of associations, b) the small sample size; c) the lack of information regarding the antihypertensive dose used, and d) the fact that the CAD diagnosis was based only on clinical history and medical file review. However, the diagnosis of CAD is initially hypothesized based on the patient's medical history; in this sense, our study simulated the conditions experienced by clinicians in their daily routine.
Conclusion
The presence of erectile dysfunction is associated with increased risk of coronary artery disease. The use of the IIEF-5 score may add information to the cardiovascular risk stratification of patients assessed at the medical office.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Sources of Funding
There were no external funding sources for this study.
Study Association
This article is the result of the Monograph for Conclusion of Medical Residence in Cardiology by Carolina Christianini Mizzaci, Rafael Modesto Fernandes, Afrânio Galdino de Araújo Junior, Paulo Oliveira Cardoso e Lucas Velloso Dutra, from Instituto Dante Pazzanese de Cardiologia - São Paulo, SP.