abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC São Paulo, SP, Brazil J7cVQ7zCQL3rfMTqwSNS56f 00016 S0066-782X2007000200016 S0066-782X(07)08800216 10.1590/S0066-782X2007000200016 Artigos Originais Prognóstico da esclerose valvar aórtica na mortalidade cardíaca de pacientes atendidos no instituto de cardiologia do Rio Grande do Sul Rosa Eduardo Maffini da Sant'anna João Ricardo Michielin Oppermann Luciana Pimentel Castro Iran Porto Alegre Rio Grande do Sul Instituto de Cardiologia do Rio Grande do Sul Fundacão Universitária de Cardiologia Brazil 02 2007 88 2 234 239 30 03 2006 19 03 2006 16 01 2006 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

OBJETIVO: Avaliar o efeito prognóstico da esclerose valvular aórtica na mortalidade e morte de causa cardíaca de pacientes atendidos no Instituto de Cardiologia do Rio Grande do Sul nos anos de 1996 a 2000. MÉTODOS: Estudo de coorte histórico que utilizou informações contidas nos bancos de dados do laboratório de ecocardiografia do Hospital de Cardiologia e nos Registros de Óbitos da Secretária da Saúde do Rio Grande do Sul. O período de avaliação foi de 1996 a 2000. Os desfechos foram morte e morte de causa cardíaca. RESULTADOS: Foram analisados 8.585 casos, dos quais 2.154 (25%) eram portadores de esclerose valvular aórtica. O tempo de seguimento médio foi de 41±6 meses, e a ocorrência de morte e morte cardíaca foram respectivamente, de 299 (3,5%) e 95 (1,1%). O grupo de pacientes com esclerose valvular aórtica apresentou mais miocardiopatia segmentar, disfunção ventricular, aumento ventricular e hipertrofia ventricular, e não apresentou, entretanto, maior risco de morte ou morte de causa cardíaca quando feita análise de multivariança. CONCLUSÃO: A presença de esclerose valvular aórtica não aumentou o risco de morte e de morte de causa cardíaca na população estudada.

 Doença das valvas cardíacas Doença das valvas cardíacas ecocardiografia 20 03 2007

ARTIGO ORIGINAL

Prognóstico da esclerose valvar aórtica na mortalidade cardíaca de pacientes atendidos no instituto de cardiologia do Rio Grande do Sul

Eduardo Maffini da RosaI; João Ricardo Michielin Sant'annaII; Luciana Pimentel OppermannIII; Iran CastroII

Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia - Porto Alegre, RS

IDoutor em Cardiologia pelo Curso de Pós-graduação da Fundação Universitária de Cardiologia

IIProfessor do Curso de Pós-graduação da Fundação Universitária de Cardiologia

IIIAluna de iniciação científica da Fundação Universitária de Cardiologia

Correspondência

RESUMO

OBJETIVO: Avaliar o efeito prognóstico da esclerose valvular aórtica na mortalidade e morte de causa cardíaca de pacientes atendidos no Instituto de Cardiologia do Rio Grande do Sul nos anos de 1996 a 2000.

MÉTODOS: Estudo de coorte histórico que utilizou informações contidas nos bancos de dados do laboratório de ecocardiografia do Hospital de Cardiologia e nos Registros de Óbitos da Secretária da Saúde do Rio Grande do Sul. O período de avaliação foi de 1996 a 2000. Os desfechos foram morte e morte de causa cardíaca.

RESULTADOS: Foram analisados 8.585 casos, dos quais 2.154 (25%) eram portadores de esclerose valvular aórtica. O tempo de seguimento médio foi de 41±6 meses, e a ocorrência de morte e morte cardíaca foram respectivamente, de 299 (3,5%) e 95 (1,1%). O grupo de pacientes com esclerose valvular aórtica apresentou mais miocardiopatia segmentar, disfunção ventricular, aumento ventricular e hipertrofia ventricular, e não apresentou, entretanto, maior risco de morte ou morte de causa cardíaca quando feita análise de multivariança.

CONCLUSÃO: A presença de esclerose valvular aórtica não aumentou o risco de morte e de morte de causa cardíaca na população estudada.

Palavras-chave: Doença das valvas cardíacas / prevenção / mortalidade, ecocardiografia.

Introdução

Os fatores etiológicos responsáveis pelo desenvolvimento da doença aterosclerótica coronariana também podem causar espessamento nos folhetos da válvula aórtica1,2. Os principais fatores são a diabete melito, a hipertensão arterial sistêmica, o tabagismo e a dislipidemia1-4,7. As semelhanças estruturais e fisiológicas entre a camada médio intimal coronariana e os tecidos que recobrem os folhetos da válvula aórtica explicam parcialmente a suscetibilidade a fatores etiológicos em comum2,4-11. A esclerose da válvula aórtica pode estar associada com a doença aterosclerótica coronariana e com maior risco de infarto ou morte de causa cardíaca3, 7,12,15.

O risco aumentado de morte cardiovascular em pacientes portadores de esclerose valvular aórtica pode ser causado pela perda progressiva da mobilidade dos folhetos valvulares aórticos e o surguimento da estenose aórtica3. Outro motivo pode ser a associação com a doença aterosclerótica coronariana3,12,13.

Otto e cols. demonstraram aumento da mortalidade e da mortalidade cardiovascular num subgrupo de pacientes com esclerose na válvula aórtica. O risco relativo de morte cardiovascular encontrado nesses pacientes foi de 1,52 (1,12 a 2,05)8. Entretanto, publicações subseqüentes questionam esses resultados, sugerindo que aspectos metodológicos justificariam os achados9-11.

A esclerose valvular aórtica foi considerada uma alteração que acompanhava o envelhecimento fisiológico, sem nenhuma outra conotação. Atualmente é vista como doença e alternativas para tratamento estão sendo pesquisadas7. As drogas inibidoras da enzima de conversão da angiotensina e da enzima hidroximetilglutaril coenzima-A redutase foram utilizadas experimentalmente para diminuir o risco de morte cardiovascular de pacientes portadores de esclerose valvular aórtica. Até o momento, existem estudos pequenos e com resultados contraditórios10,11,16-20.

O objetivo do nosso estudo é avaliar o efeito da esclerose valvular aórtica na mortalidade por todas as causas e mortalidade cardíaca de pacientes atendidos no Instituto de Cardiologia do Rio Grande do Sul (IC-FUC).

Métodos

Estudo de coorte realizado com pacientes ambulatoriais do hospital IC-FUC Instituto de Cardiologia do Rio Grande do Sul, no período de janeiro de 1996 a dezembro de 2000. Os critérios de inclusão foram: pacientes que realizaram ecocardiograma no IC-FUC, no período de janeiro de 1996 a dezembro de 2000, com idade superior a 50 anos no momento do exame de ecocardiografia e residentes no Estado do Rio Grande do Sul. Os critérios de exclusão foram: prótese valvular aórtica ou mitral, insuficiência valvular mitral ou aórtica de gravidade moderada ou severa, cardiopatia reumática, cardiopatia congênita, cirurgia cardíaca valvular, estar em tratamento de hemodiálise, miocardiopatia hipertrófica septal assimétrica, estenose aórtica, ou presença de patologias que limitem a vida por um período menor de seis meses.

Foram identificados pacientes no banco de dados do serviço de ecocardiografia do IC-FUC segundo critérios de inclusão e exclusão. Os pacientes selecionados foram identificados no Banco de Óbitos da Secretária da Saúde do Rio Grande do Sul. O fator em estudo foi a presença de esclerose valvular aórtica. Os desfechos examinados foram: morte ou morte de origem cardíaca. Foi considerada morte por motivo cardíaco quando o atestado de óbito apresentava: infarto agudo do miocárdio, angina, miocardiopatia isquêmica, choque cardiogênico, ou morte súbita.

As variáveis em avaliação foram: sexo, idade, disfunção ventricular, miocardiopatia segmentar, hipertrofia ventricular esquerda e aumento ventricular.

Médicos ecocardiografistas qualificados realizaram os exames de ecocardiografia transtorácica uni e bimensional, Doppler pulsado e contínuo e mapeamento de fluxo a cores. Foram utilizados os seguintes equipamentos: Sonus 1.000, ATL HDI 5000 CV, Philips Medical Systems 25000 e 5500. Os transdutores empregados eram mecânicos e eletrônicos, com freqüência de 2,5 megaHertz.

A esclerose valvular aórtica foi diagnosticada pelo espessamento da borda de uma das cúspides da válvula aórtica, sem aumento do gradiente ventricular esquerdo-aorta. Miocardiopatia segmentar estava presente se acinesia, discinesia ou hipocinesia segmentar fossem detectadas em exame de ecocardiografia. Cardiopatia reumática foi diagnosticada atendendo a critérios ecocardiográficos. O diagnóstico de hipertrofia ventricular esquerda foi feito quando a espessura da parede septal ou livre do ventrículo esquerdo era superior a 11mm. O aumento ventricular foi definido como diâmetro sistólico maior de 36mm ou diâmetro diastólico maior de 55mm. A disfunção ventricular foi diagnosticada para fração de ejeção menor que 45%, método de Teichholz.

A análise estatística foi realizada com o pacote estatístico SPSS. Os testes usados foram: risco relativo, intervalos de confiança, análise multivariada de Cox e curva de Kaplan e Mayer.

Resultados

No período de 1996 a 2000 foram avaliados 8.585 casos, dos quais 2.154 (25%) eram portadores de esclerose valvular aórtica. A média de idade dos pacientes da amostra foi de 56 anos, e o tempo de seguimento médio foi de 41 meses. A mortalidade ocorreu em 299 (3,5%) casos; em 95 (1,1%) a causa foi cardíaca. As demais variáveis: sexo, miocardiopatia segmentar, disfunção ventricular e aumento ventricular estão descritas na tabela 1.

A distribuição, segundo a presença de esclerose valvular aórtica, das variáveis: idade, sexo, miocardiopatia segmentar, disfunção ventricular, aumento ventricular, hipertrofia ventricular esquerda, exame normal, tempo de seguimento no estudo, número de mortes e de mortes de causa cardíaca estão na tabela 2. Os pacientes portadores de esclerose valvular aórtica possuíam mais miocardiopatia segmentar (16,2% X 7,5%, p<0,001), disfunção ventricular ( 17,2% X 10,4%, p<0,001), hipertrofia ventricular (23,1% X 10,9%, p<0,001) que os controles sem esclerose valvular aórtica. No grupo de pacientes portadores de esclerose valvular aórtica também foi observada idade mais avançada (67,87±10,43 X 50,72±15,16, p<0,001) e maior mortalidade (6% X 2,6%, p<0,001) que nos controles.

Na tabela 3 estão descritas as comparações entre os pacientes que morreram e os sobreviventes até o término do seguimento. No grupo de pacientes que morreram, a presença de esclerose valvular aórtica (49,4% X 24,3%, p<0,001), o sexo masculino (52,9% X 41,8%, p<0,001), a média de idade (66,44±14,63 X 54,62±15,52 em anos, p<0,001), a miocardiopatia segmentar (20,9% X 9,3%, p<0,001), a disfunção ventricular (30,8% X 11,4%, p<0,001), o aumento ventricular (15,6% X 5,7%, p<0,001) e a hipertrofia ventricular (24% X 13,5%, p<0,0001) foram mais freqüentes que no grupo de sobreviventes. O tempo de seguimento (18,72±13,56 X 42,54±3,34 em meses, p<0,001) e os casos com exame ecocardiográfico normal (8% X 29,3%) foram menores e menos freqüentes nos pacientes que foram a óbito que nos pacientes que não morreram, respectivamente. Quando a análise é repetida para morte de causa cardíaca (tab. 4), o comportamento das variáveis se repete.

A esclerose valvular aórtica não apresenta efeito prognóstico na mortalidade (RR- 1,04, IC- 0,78- 1,38) e morte de causa cardíaca (RR- 1,38, IC- 0,85-2,24) quando analisada pelo teste de multivariança de Cox (tabs. 5 e 6, figs. 1 e 2). As variáveis: idade, miocardiopatia isquêmica, disfunção ventricular, aumento ventricular e hipertrofia ventricular aumentaram a ocorrência de morte. A variável sexo masculino foi estatisticamente significante quando testada para morte (tabs. 5 e 6).

Discussão

Em nosso estudo não verificamos aumento do risco de morte ou morte de causa cardíaca em pacientes portadores de esclerose valvular aórtica, o que contraria resultados de alguns estudos publicados3,4, 6,15,21-28.

Os registros presentes na literatura referentes à associação da esclerose valvular aórtica com doença arterial coronariana ou com eventos isquêmicos coronarianos são contraditórios, variando desde publicações que sugerem aumento de 50% na mortalidade cardiovascular, até as que demonstram existir associação com doença arterial coronariana e recomendações para uso de prevenção secundária com estatinas ou inibidores da enzima de conversão da angiotensina em pacientes com esclerose valvular aórtica29-47. No outro extremo, Chandra e cols. não encontraram associação entre a esclerose valvular aórtica e desfechos de morte ou morte de causa cardiovascular48 e Tolstrup e cols. não observaram associação de esclerose valvular aórtica com doença arterial coronariana49. Em nosso estudo, foram obtidas evidências de associação entre esclerose valvular aórtica e miocardiopatia segmentar, mas não tivemos associação independente com a ocorrência de morte. A doença aterosclerótica coronariana tem aspectos etiopatogênicos em comum com a esclerose da válvula aórtica, porém não está clara a associação da presença de esclerose valvular aórtica com o desencadeamento de instabilidade do endotélio coronariano.

O estudo de Otto e cols. é um referencial sobre o efeito prognóstico da esclerose valvular aórtica na mortalidade geral e cardiovascular. Neste estudo foi demonstrado que a esclerose valvular aórtica não influi no prognóstico dos pacientes, com exceção de um subgrupo de pacientes constituído pela ausência da cardiopatia isquêmica1. Os resultados obtidos no presente estudo estão em acordo com os achados de Otto e cols., pois a nossa amostra foi composta por casos com e sem miocardiopatia segmentar, o que justifica não termos encontrado efeito prognóstico. Desse modo, supomos que se fosse feito um estudo para avaliar primariamente o efeito prognóstico da esclerose valvular aórtica em pacientes sem cardiopatia isquêmica, possivelmente seriam obtidos resultados positivos.

A desproporcionalidade da ocorrência de miocardiopatia segmentar, miocardiopatia hipertensiva, disfunção ventricular e aumento ventricular apresentada na tabela 2, não corresponde a um viés de seleção. O grande número de casos incluídos em nosso estudo permite levantar a hipótese de que a desproporcionalidade não ocorre ao acaso, mas que existe associação entre esclerose valvular aórtica e miocardiopatia hipertensiva, disfunção ventricular e aumento ventricular, como ocorre com a cardiopatia isquêmica.

Os principais fatores não-mensurados que poderiam impor limitações aos resultados encontrados foram: a indeterminação da duração da esclerose valvular aórtica no momento de entrada dos pacientes no estudo, o modo utilizado para inferir o diagnóstico de coronariopatia, ou seja, limitado à presença de miocardiopatia segmentar na ecocardiografia, a maneira utilizada para considerar os pacientes como vivos no termino do estudo (não presentes na lista de óbitos na Secretaria da Saúde), e a veracidade das informações oriundas dos atestados de óbito. Outra possibilidade de viés é a falta de informações nos bancos de dados referente ao uso de medicamentos como vastatinas e inibidores da enzima de conversão que eventualmente pudessem interferir nos resultados.

Em conclusão, os achados demonstram que pacientes portadores de esclerose da válvula aórtica na população em estudo, não apresentaram aumento do risco de morte ou morte de causa cardíaca, porém novos estudos são necessários para confirmação destes dados.

Trabalho realizado com apoio parcial da Fundação de Amparo a Pesquisa no Rio Grande do Sul (FAPERGS).

Potencial Conflito de Interesses

Declaro não haver conflitos de interesses pertinentes.

Eduardo Maffini da Rosa

Rua Faustino de Biasin, 375/32

95052-250 – Caxias do Sul, RS

E-mail:

emaffini@cardiol.br

Iran Castro

Av. Princesa Isabel, 395

90620-001- Porto Alegre, RS

Email: icastro@cardiol.br

Artigo recebido em 16/01/06; revisado recebido em 19/03/06; aceito em 30/03/06.

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Chlamydia pneumoniae exposure and inflammatory markers in acute coronary syndrome (CIMACS) Am J Cardiol. 2001 214 8 88 Chandra HR Choudhary N O’Neill C Boura J Timmis GC O’Neill WW 34. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995; 92: 657-71. Coronary plaque disruption Circulation. 1995 657 71 92 Falk E Shah PK Fuster V 35. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000; 102: 2165-8. Direct proinflammatory effect of C-reactive protein on human endothelial cells Circulation. 2000 2165 8 102 Pasceri V Willerson JT Yeh ET 36. Prasad Y, Bhalodkar NC. Aortic sclerosis: a marker of coronary atherosclerosis. Clin Cardiol. 2004; 27: 671-3. Aortic sclerosis: a marker of coronary atherosclerosis Clin Cardiol. 2004 671 3 27 Prasad Y Bhalodkar NC 37. Poggianti E, Venneri L, Chubuchny V, Jambrik Z, Baroncini LA, Picano E. 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Cardiology. 2002; 98: 154-8. Morphologic characteristics of aortic valve sclerosis by transesophageal echocardiography: importance for the prediction of coronary artery disease Cardiology. 2002 154 8 98 Tolstrup K Crawford MH Roldan CA Original Articles Prognosis of aortic valve sclerosis in cardiovascular mortality of patients seen at the cardiology institute of Rio Grande do Sul

OBJECTIVE: To evaluate the prognostic effect of aortic valve sclerosis on all-cause and cardiovascular mortality of patients seen at the Cardiology Institute of the Brazilian state of Rio Grande do Sul from 1996 to 2000. METHODS: A historical cohort study using information from both the database of the Echocardiography Laboratory of the Cardiology Hospital and the Death Registry of Rio Grande do Sul Health Department. The evaluation was carried out from 1996 to 2000. Study endpoints were all-cause and cardiovascular mortality. RESULTS: A total of 8585 patients were analyzed, 2154 (25%) of whom had aortic valve sclerosis. Mean follow-up was 41±6 months, and all-cause and cardiovascular deaths were 299 (3.5%) and 95 (1.1%), respectively. The group of patients with aortic valve sclerosis had more segmental cardiomyopathy, ventricular dysfunction, ventricular enlargement, and ventricular hypertrophy; yet, they did not show higher risk for all-cause or cardiovascular mortality in the multivariate analysis. CONCLUSION: The presence of aortic valve sclerosis was not associated with increased risk for all-cause and cardiovascular mortality in the population studied.

 Heart valve desease Heart valve desease echocardiography

ORIGINAL ARTICLE

Prognosis of aortic valve sclerosis in cardiovascular mortality of patients seen at the cardiology institute of Rio Grande do Sul

Eduardo Maffini da RosaI; João Ricardo Michielin Sant'annaII; Luciana Pimentel OppermannIII; Iran CastroII

Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia - Porto Alegre, RS - Brazil

IDoutor em Cardiologia pelo Curso de Pós-graduação da Fundação Universitária de Cardiologia

IIProfessor do Curso de Pós-graduação da Fundação Universitária de Cardiologia

IIIAluna de iniciação científica da Fundação Universitária de Cardiologia

Mailing Address

SUMMARY

OBJECTIVE: To evaluate the prognostic effect of aortic valve sclerosis in mortality and cardiac death of patients assisted at the Cardiology Institute of the Brazilian state of Rio Grande do Sul from 1996 to 2000.

METHODS: A historical cohort study using information from both the database of the Echocardiography Laboratory of the Cardiology Hospital and the Death Registry of Rio Grande do Sul Health Department. The evaluation was carried out from 1996 to 2000. Study endpoints were death and cardiac death.

RESULTS: A total of 8585 patients were analyzed, 2154 (25%) of whom had aortic valve sclerosis. Mean follow-up was 41± 6 months, and death and cardiac death were 299 (3.5%) and 95 (1.1%), respectively. The group of patients with aortic valve sclerosis had more segmental cardiomyopathy, ventricular dysfunction, ventricular enlargement, and ventricular hypertrophy; yet, they did not show higher risk for death or cardiac death in the multivariate analysis.

CONCLUSION: The presence of aortic valve sclerosis was not associated with increased risk for death and cardiac death in the population studied.

Key words: Heart valve diseases / prevention / mortality; echocardiography.

Introduction

The etiological factors underlying the development of coronary atherosclerosis may also cause aortic valve leaflet thickening1,2. Among them, diabetes mellitus, hypertension, smoking, and dyslipidemia are thought to play a leading role1-4,7. The structural and physiological similarities shared by the coronary intimal-medial layer and the tissues overlying aortic valve leaflets explain, in part, their susceptibility to common etiological factors2,4-11. Aortic valve sclerosis (AVS) may be associated with coronary atherosclerosis and greater risk for myocardial infarction or cardiovascular death3, 7,12,15.

The greater risk for cardiovascular death in AVS patients may be related to a progressive loss of aortic leaflet mobility and the development of aortic stenosis3. The association with coronary atherosclerosis may be also implicated3,12,13.

Otto and colleagues have demonstrated increased all-cause and cardiovascular mortality in a subgroup of patients with sclerotic aortic valves. The relative risk of cardiovascular death found in these patients was 1.52 (1.12 to 2.05)8. Nevertheless, later reports called these results into question, suggesting that methodological aspects would justify these findings9-11.

Aortic valve sclerosis was regarded as a change brought on by normal aging, with no other connotation. Currently, it is considered a disease, and alternative treatments are being sought7. Angiotensin-converting-enzyme inhibitors and hydroxymethylglutaryl-coenzyme A reductase inhibitors were used experimentally to reduce the risk of cardiovascular death of patients with aortic valve sclerosis. Thus far, only small and contradictory studies exist10,11,16-20.

This study was meant to evaluate the effect of aortic valve sclerosis on all-cause and cardiovascular mortality of patients seen at the Cardiology Institute of Rio Grande do Sul (IC-FUC).

Methods

A cohort study comprising patients seen at the IC/FUC from January 1996 to December 2000. Inclusion criteria were patients older than 50 living in the state of Rio Grande do Sul who underwent echocardiography at the IC-FUC from January 1996 to December 2000. Exclusion criteria were mitral or aortic valve prosthesis, moderate to severe mitral or aortic regurgitation, rheumatic heart disease, congenital heart disease, heart valve surgery, ongoing hemodialysis treatment, hypertrophic cardiomyopathy (asymmetric septal hypertrophy), aortic stenosis, or the presence of diseases that reduce life expectancy to less than six months.

Patients were selected from the database of the IC-FUC Echocardiography Division, according to the inclusion and exclusion criteria, and from the Death Registry of Rio Grande do Sul Health Department. Central to this study was the presence of aortic valve sclerosis. Study endpoints were all-cause or cardiovascular death. Cardiovascular death was considered with the death certificate reported acute myocardial infarction, angina pectoris, ischemic cardiomyopathy, cardiogenic shock, or sudden death.

The following variables were analyzed: gender, age, ventricular dysfunction, segmental cardiomyopathy, left ventricular hypertrophy, and ventricular enlargement.

Qualified echocardiographers, who were also medical doctors, performed one- and two-dimensional transthoracic echocardiograms, pulsed and continuous wave Doppler, and color Doppler flow mapping. The following devices were used: Sonus 1000, ATL HDI 5000 CV, Philips Medical Systems 25000 and 5500, equipped with 2.5 MHz mechanical and electronic transducers.

Aortic valve sclerosis was diagnosed by the thickening of one of the valve cusps on its border, without increase in the left ventricular-aortic gradient. Segmental cardiomyopathy was determined in the presence of segmental akinesia, dyskinesia or hypokinesia on the echocardiogram. Rheumatic heart disease was diagnosed according to echocardiographic criteria. The diagnosis of left ventricular hypertrophy was made when LV septal or free wall thickness exceeded 11 mm. Ventricular enlargement was defined as systolic diameter > 36 mm or diastolic diameter > 55 mm. Ventricular dysfunction was defined as ejection fraction < 45%, using the Teichholz method.

Statistical analysis was performed using SPSS statistical software. The following tests were applied: relative risk, confidence intervals, Cox multivariate analysis, and Kaplan-Meier curve.

Results

Between 1996 and 2000, 8585 patients were assessed, of whom 2154 (25%) had aortic valve sclerosis. Mean age of patients was 56, and mean follow-up period was 41 months. Two hundred and ninety-nine patients died (3.5%), 95 (1.1%) of them from cardiovascular cause. The other variables, namely, gender, segmental cardiomyopathy, ventricular dysfunction, and ventricular enlargement, are described in table 1.

Table 2 shows the distribution of the following variables, according to the presence of aortic valve sclerosis: age, gender, segmental cardiomyopathy, ventricular dysfunction, ventricular enlargement, left ventricular hypertrophy, normal examination, mean follow-up, and number of all-cause and cardiovascular deaths. AVS patients showed higher rates of segmental cardiomyopathy (16.2% vs. 7.5%, p<0.001), ventricular dysfunction (17.2% vs. 10.4%, p<0.001), and ventricular hypertrophy (23.1% vs. 10.9%, p<0.001) than non-AVS controls. In addition, patients in the AVS group were found to be older (67.87 ± 10.43 vs. 50.72 ± 15.16, p<0.001) and to have a higher mortality rate (6% vs. 2.6%, p<0.001) than the control group.

In table 3 comparisons are made between patients who died and those who survived by the end of the follow-up period. In the group of patients who died, the presence of aortic valve sclerosis (49.4% vs. 24.3%, p<0.001), male gender (52.9% vs. 41.8%, p<0.001), mean age (6.44 ± 14.63 vs. 54.62 ± 15.52 in years, p<0.001), segmental cardiomyopathy (20.9% vs. 9.3%, p<0.001), ventricular dysfunction (30.8% vs. 11.4%, p<0.001), ventricular enlargement (15.6% vs. 5.7%, p<0.001), and ventricular hypertrophy (24% vs. 13.5%, p<0.001) was more frequent than in the survivor group. Follow-up period was lower (18.72 ± 13.56 vs. 42.54 ± 3.34 in months, p<0.001), and normal echocardiographic examination (8% vs. 29.3%) was less frequent in patients who died than in those who survived, respectively. When the analysis is repeated for cardiovascular death (Tab. 4), these variables showed the same behavior.

Aortic valve sclerosis has no prognostic effect on all-cause (RR 1.04, CI 0.78-1.38) and cardiovascular (RR 1.38, CI 0.85-2.24) mortality by the Cox multivariate analysis (Tabs. 5 and 6, Figs. 1 and 2). The following variables were associated with higher mortality rate: age, ischemic cardiomyopathy, ventricular dysfunction, ventricular enlargement, and ventricular hypertrophy. Male sex was statistically significant when tested for death (Tabs. 5 and 6).

Discussion

In our study, the presence of aortic valve sclerosis was not associated with increased risk for all-cause and cardiovascular mortality, which contradicts the results of some published studies3, 4, 6, 15, 21-28.

Literature data on the association of aortic valve sclerosis with coronary artery disease or coronary ischemic events are controversial, ranging from reports suggesting a 50% increase in cardiovascular mortality to those demonstrating an association with coronary artery disease to recommendations for secondary prevention with statins or angiotensin-converting enzymes in AVS patients29-47. At the other extreme, Chandra and colleagues found no association between aortic valve sclerosis and the all-cause or cardiovascular mortality endpoint48, and Tolstrup et al found no association between aortic valve sclerosis and coronary artery disease49. In our study, there was evidence of association between aortic valve sclerosis and segmental cardiomyopathy, but no independent association with death was observed. Coronary atherosclerosis and aortic valve sclerosis share common etiopathogenic features, but we have not grasped how to associate the presence of aortic valve sclerosis with the development of coronary endothelial instability.

The study by Otto et al represents a reference regarding the prognostic effect of aortic valve sclerosis on overall and cardiovascular mortality. In this study, aortic valve sclerosis did not influence patients’ prognosis, with the exception of a subgroup of patients with no ischemic heart disease1. Our findings are consistent with those of Otto et al, because our sample comprised patients with and without segmental cardiomyopathy, which explains the lack of a prognostic effect. Therefore, we suppose that if a study were carried out to evaluate primarily the prognostic effect of aortic valve sclerosis in patients with no ischemic heart disease, it is likely that positive results would be obtained.

The disproportionate occurrence of segmental cardiomyopathy, hypertensive cardiomyopathy, ventricular dysfunction, and ventricular enlargement presented in table 2 is not due to any selection bias. The large number of cases included in our study allows hypothesizing that this disproportion is not accidental, but rather that an association exists between aortic valve sclerosis and hypertensive cardiomyopathy, ventricular dysfunction, and ventricular enlargement, as with ischemic heart disease.

The major non-measured factors that could limit our findings are the fact that the time elapsed since AVS onset was not defined at study entry; the method used to infer the diagnosis of heart disease, that is, restricted to the presence of segmental cardiomyopathy on the echocardiogram; the method used to consider patients as survivors at study conclusion, that is, the fact that they were not included in the death registry of the Health Department; and the reliability of information abstracted from death certificates. Another potential source of bias is the lack of information in the database regarding the use of drugs such as vastatin and ACE inhibitors, which could eventually influence the results.

In conclusion, our findings indicate that, in this study, AVS patients did not face higher risk of all-cause or cardiovascular mortality; yet, further studies are warranted to replicate these data.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

References

Eduardo Maffini da Rosa

Rua Faustino de Biasin, 375/32

95052-250 – Caxias do Sul, RS - Brazil

E-mail:

emaffini@cardiol.br

Iran Castro

Av. Princesa Isabel, 395

90620-001- Porto Alegre, RS - Brazil

Email: icastro@cardiol.br

Manuscript received January 16, 2006; revised manuscript received March 19, 2006; accepted March 30, 2006.