DENIS CARLOS DOS SANTOS · ... Questionário de Comorbidades e consumo de medicamentos ... o ritmo...

Londrina 2012

CENTRO DE PESQUISA EM CIÊNCIAS DA SAÚDE MESTRADO EM CIÊNCIAS DA REABILITAÇÃO

DENIS CARLOS DOS SANTOS

ANÁLISE DA FUNÇÃO RESPIRATÓRIA DE IDOSOS

FISICAMENTE INDEPENDENTES USUÁRIOS DE

INIBIDORES DA ENZIMA CONVERSORA DE

ANGIOTENSINA

Londrina 2012





ANGIOTENSINA

Trabalho apresentado ao Programa de Pós-Graduação em Ciências da Reabilitação (Programa Associado entre Universidade Estadual de Londrina - UEL e Universidade Norte do Paraná - UNOPAR), como requisito para obtenção do título de Mestre em Ciências da Reabilitação.

Orientador: Profª. Drª. Karen Barros Parron Fernandes. Co-Orientadora: Profª. Drª. Eliane Regina Ferreira Sernache de Freitas.





ANGIOTENSINA

Trabalho apresentado ao Programa de Pós-Graduação em Ciências da Reabilitação (Programa Associado entre Universidade Estadual de Londrina - UEL e Universidade Norte do Paraná - UNOPAR), como requisito para obtenção do título de Mestre em Ciências da Reabilitação.

BANCA EXAMINADORA

____________________________________ Profª. Drª. Karen Barros Parron Fernandes

Universidade Norte do Paraná

____________________________________ Profª. Drª. Vanessa Suziane Probst

Universidade Norte do Paraná

____________________________________ Profª. Drª. Gislaine Garcia Pelosi Gomes

Universidade Estadual de Londrina

Londrina, 27 de fevereiro de 2012.

AUTORIZO A REPRODUÇÃO TOTAL OU PARCIAL DESTE TRABALHO, POR QUALQUER MEIO CONVENCIONAL OU ELETRÔNICO, PARA FINS DE ESTUDO E PESQUISA, DESDE QUE CITADA A FONTE.

Dados Internacionais de catalogação-na-publicação Universidade Norte do Paraná

Biblioteca Central

Setor de Tratamento da Informação

Santos, Denis Carlos dos.

S233e Análise da função respiratória de idosos fisicamente independentes usuários

de inibidores da enzima conversora de angiotensina / Denis Carlos dos Santos.

Londrina : [s.n], 2012.

xii; 84p.

Dissertação (Mestrado). Ciências da Reabilitação. Universidade Norte do

Paraná.

Orientadora: Profª Drª. Karen Barros Parron Fernandes

1- Ciências da reabilitação - dissertação de mestrado – UNOPAR/UEL 2-

Inibidores da enzima conversora de angiotensina II 3- Força muscular respiratória

4- Função pulmonar 5- Idoso I- Fernandes, Karen Barros Parron, orient. II-

Universidade Norte do Paraná. III- Universidade Estadual de Londrina.

CDU 615.816

DEDICATÓRIA

A minha esposa Jaqueline Kellyn Dias de

Almeida, pela compreensão e paciência

nos momentos de ausência e abdicações

e por todo amor, dedicação, apoio e

estímulo recebidos.

Aos meus pais José Francisco (in

memoriam) e Izabel Cristina pela vida,

pelo amor incondicional e por toda a

dedicação.

AGRADECIMENTOS

À querida mestre Profa. Dra. Karen Barros Parron Fernandes:

Vivemos uma escassez de pessoas honestas, sensatas e humildes.

Alie-se a isso, a falta de pessoas inteligentes e competentes, determinadas e

ousadas, persistentes e discretas, acadêmicas e pesquisadoras, carinhosas e

respeitadoras... Você, minha querida mestre e amiga, consegue conciliar todas estas

qualidades em uma só pessoa. Como orientado, agradeço pela forma como

conseguiu ampliar minha visão em relação à ciência e pesquisa e pela brilhante

orientação. Como amigo, só posso dizer que hoje me sinto ainda mais privilegiado

em poder fazer parte da sua vida. Serei eternamente grato pela forma que estendeu

vossas mãos, quando precisei, mesmo sem me conhecer. Meu muito obrigado, de

coração.

À Profa. Dra. Eliane Regina Ferreira Sernache de Freitas, minha co-

orientadora, obrigado por ter aceitado participar desta caminhada, pela

disponibilidade em todos os momentos e pelas valiosas sugestões.

À Profa. Dra. Vanessa Suziane Probst, que com a maturidade e

clareza do seu fazer científico, esteve sempre pronta a solucionar minhas dúvidas,

esclarecendo cada passo desde trabalho.

Aos amigos Vinícius Arantes Coelho, João Paulo Manfré dos Santos

e Luiz Lúcio de Carvalho que estiveram presentes em todos os momentos dessa

batalha, partilhando de alegrias, tristezas, tensões e satisfações. Amizade surgida

com o mestrado, persistindo por toda a vida.

Aos irmãos Lilian, Sheila e Danilo, pelo companheirismo e amor.

Aos sobrinhos, Wendel, Isabella, Gabriela e Mariana.

Aos demais professores, colegas e colaboradores, que me

auxiliaram no decorrer do curso.

"Não sei o que possa parecer aos olhos do

mundo, mas aos meus pareço apenas ter sido

como um menino brincando à beira-mar,

divertindo-me com o fato de encontrar de vez

em quando um seixo mais liso ou uma concha

mais bonita que o normal, enquanto o grande

oceano da verdade permanece completamente

por descobrir à minha frente."

Isaac Newton

SANTOS, Denis Carlos dos. Análise da função respiratória de idosos fisicamente independentes usuários de inibidores da enzima conversora de angiotensina. 84 f. Dissertação (Mestrado em Ciências da Reabilitação) – Universidade Norte do Paraná, Londrina, 2012.

RESUMO

A terapia com inibidores da enzima conversora de angiotensina (IECA) melhora a capacidade e tolerância ao exercício e a força muscular respiratória em indivíduos com insuficiência cardíaca congestiva. Contudo, estudos adicionais a respeito destes efeitos em indivíduos idosos saudáveis ainda não foram realizados. O objetivo deste estudo foi verificar os efeitos do uso crônico de IECA sobre a força muscular respiratória e a função pulmonar de idosos fisicamente independentes. Neste estudo retrospectivo, foram selecionados 252 indivíduos idosos do projeto EELO (Estudo sobre Envelhecimento e Longevidade), residentes em Londrina-PR. Os pacientes selecionados foram agrupados em três categorias de acordo com a medicação utilizada: I) Grupo experimental: pacientes usando IECA há pelo menos seis meses (GIECA), II) Grupo controle: pacientes idosos sem comprometimento da função pulmonar (GC) e III) Pacientes usuários de Bloqueadores dos Receptores de Angiotensina II (GBRA). A força muscular respiratória (avaliada pela pressão inspiratória máxima: PIMAX e pressão expiratória máxima: PEMax) foi medida por meio de manovacuometria, enquanto a função pulmonar foi analisada por espirometria simples, considerando as seguintes variáveis: capacidade vital forçada (CVF), volume expiratório forçado no primeiro segundo (VEF1) e a razão entre o VEF1 e a CVF (VEF1/CVF). Todas as variáveis do estudo foram representadas com porcentagem do valor predito, corrigido para a população brasileira. A PImax foi maior nos grupos GIECA e GBRA, comparados ao GC (102,2%pred.; 109,7%pred.; 93,2%pred., respectivamente), de acordo com o teste de Kruskal-Wallis, seguido pelo pós teste de Dunn (p=0,001). A PEmax foi maior no GIECA, comparado aos GBRA e GC (119,9%pred.; 103,7%pred.; 103,1%pred.; respectivamente), de acordo com o teste de Kruskal-Wallis, seguido pelo pós teste de Dunn (p=0,003). Além disso, o GIECA apresentou maior CVF (GIECA: 92,47%pred.; GC: 86,65%pred.; GBRA: 87,87%pred.; p=0,010), maior VEF1(GIECA: 97%pred.; GC: 90,5%pred.; GBRA: 89%pred., p=0,001) e maior relação VEF1/CVF (GIECA: 106%; GC: 102%; GBRA:106,5%, p=0,003), que o GC, contudo sem diferenças em relação ao GBRA. Por outro lado, o grupo GBRA não apresentou diferença na função pulmonar em relação ao GC. Desta forma, pode-se concluir que idosos usuários de IECA apresentam maior força muscular e melhor função pulmonar quando comparados a idosos que não utilizam esta medicação.

Palavras-chave: Inibidores da Enzima Conversora de Angiotensina II. Força Muscular Respiratória. Função pulmonar. Idoso.

SANTOS, Denis Carlos dos. Analysis of respiratory function of physically independent elderly using angiotensin-converting-enzyme inhibitors. 84p. Dissertação (Mestrado em Ciências da Reabilitação) – Universidade Norte do Paraná, Londrina, 2012.

ABSTRACT

Studies have reported that treatment with angiotensin-converting enzyme inhibitors (ACEI) improve exercise capacity and tolerance as well as respiratory function in patients with congestive heart failure. However, additional studies concerning its effects in elderly have not been addressed. The aim of this study was to investigate the effects of long-term ACEI therapy on respiratory function in physically independent elderly. For this retrospective cross-sectional study, patients were randomly selected from an ageing study (EELO project) performed in Londrina, Brazil. The selected subjects were grouped into three categories according to the medication usage: I) patients using ACEI for at least six months were referred as experimental group (ACEIG), II) elder patients with normal pulmonary function, referred as control group (CG) and III) Angiotensin-II Receptor Blockers (ARBG). Respiratory muscle strength was assessed by measuring maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) using manovacuometer while pulmonary function was evaluated by spirometry (considering the following variables: FVC, FEV1, FEV1/FVC ratio). All the variables were presented as % of predicted values, corrected for Brazilian population. ACEIG (102.2%) and ARBG (109.7%) showed higher values for MIP when compared to control group (CG: 93.2%), according to Kruskall-Walis’ test (p=0.001). Similar results were observed considering the MEP (ACEIG: 119.9%pred.; ARBG: 103.7%pred.; CG:103.1%pred, p=0.003). Moreover, the ACEIG showed higher FVC (ACEIG: 92.47%pred.; CG: 86.65%pred.; ARBG: 87.87%pred.; p=0.010), higher FEV1(ACEIG: 97%pred.; CG: 90.5%pred.; ARBG: 83.25%pred., p=0.001) and higher FEV1/FVC (ACEIG: 106%; CG: 102%; ARBG:106.5%, p=0.003) than control group. However, the ARBG was similar to ACEIG and CG regarding lung function. According to these results, ACEI therapy seems to be related with better respiratory muscle strength and pulmonary function in physically independent elderly. Key words: Angiotensin-Converting Enzyme Inhibitors. Respiratory Muscle Strength. Pulmonary Function. Elderly.

LISTA DE ILUSTRAÇÕES

Figure 1 - Flowchart of the population enrolled at the study after inclusion/exclusion

criteria …………....................................................................................................... 46

LISTA DE TABELAS

Table 1 – Distribution of anthropometric data among groups................................ 47 Table 2 – Comparison of the respiratory muscle strength among groups............. 48 Table 3 –Comparison of data pulmonary function among groups.......................... 49

LISTA DE ABREVIATURAS E SIGLAS

BRA Bloqueadores dos Receptores da Angiotensina II

CRF Capacidade Residual Funcional

CVF Capacidade Vital Forçada

DPOC Doença Pulmonar Obstrutiva Crônica

ECA Enzima Conversora de Angiotensina

EELO Estudo do Envelhecimento e Longevidade

IECA Inibidores da Enzima Conversora de Angiotensina

GC Grupo Controle

GBRA Grupo usuários de Bloqueadores dos Receptores da Angiotensina II

GIECA Grupo usuários de Inibidores da Enzima Conversora de Angiotensina

PEmax Pressão Expiratória Máxima

PImax Pressão Inspiratória Máxima

PNAD Pesquisa Nacional por Amostra de Domicílios

PSF Programa Saúde da Família

UBSs Unidades Básicas de Saúde

SBPT Sociedade Brasileira de Pneumologia e Tisiologia

SRAA Sistema Renina-Angiotensina-Aldosterona

V/Q Relação entre Ventilação e Perfusão

VEF1 Volume Expiratório Forçado no Primeiro Segundo

VEF1/CVF Razão do Volume Expiratório Forçado no primeiro segundo (VEF1) e da

Capacidade Vital Forçada (CVF)

VO2 max Volume de Oxigênio Máximo

VO2 submax Volume de Oxigênio Submáximo

SUMÁRIO

1 INTRODUÇÃO ....................................................................................................... 13

2 REVISÃO DE LITERATURA - CONTEXTUALIZAÇÃO ........................................ 15

2.1 PROCESSO DE ENVELHECIMENTO ............................................................................15

2.2 ENVELHECIMENTO DO SISTEMA RESPIRATÓRIO ....................................................... 16

2.3 DOENÇAS CRÔNICO-DEGENERATIVAS E CONSUMO DE MEDICAMENTOS EM IDOSOS ......19

2.4 INIBIDORES DA ENZIMA CONVERSORA DE ANGIOTENSINA (IECA) ...............................20

2.4.1 Classificação e Mecanismo de Ação .............................................................. 20

2.4.2 Efeitos Farmacológicos e Indicação Clínica .....................................................23

2.4.3 Efeito dos IECA na Força Muscular Respiratória e Função Pulmonar ............23

3 ARTIGO ................................ ................................................................................. 26

4. CONCLUSÃO GERAL .......................................................................................... 50

5. REFERÊNCIAS ..................................................................................................... 51

6. APÊNDICE ............................................................................................................ 60

APÊNDICE A – Questionário de Comorbidades e consumo de medicamentos ....... 61

7. ANEXOS ............................................................................................................... 63

ANEXO A – Parecer do Comitê de Ética em Pesquisa da UNOPAR ........................ 64

ANEXO B – Normas de formatação do periódico Journal of the American Geriatrics

Society ..................................................................................................................... 65

13

1 INTRODUÇÃO

Atualmente, uma das ansiedades que a sociedade moderna

enfrenta relaciona-se diretamente com o processo de envelhecimento, uma vez que

se observa um aumento considerável da população idosa em relação aos demais

grupos etários em todo o mundo1-3. No Brasil, o ritmo de crescimento da população

idosa tem sido sistemático e consistente. Segundo a Pesquisa Nacional por Amostra

de Domicílios – PNAD, o país conta com uma população de cerca de 21 milhões de

pessoas de 60 anos ou mais de idade4.

O processo de envelhecimento afeta cada célula, tecido e órgão. As

alterações são decorrentes de uma combinação de fatores tais como: fatores

genéticos, apectos ambientais, aspectos nutricionais e estilo de vida5-7, ocasionando

modificações em todos os sistemas corpóreos.

O sistema respiratório sofre modificações anátomo-funcionais

inerentes ao processo de envelhecimento, embora estas possam variar de

amplitude5. Similarmente, a função pulmonar também é afetada com deterioração

tanto das medidas estáticas quanto dinâmicas5;7-9, sendo que, até a idade de 25

anos, não são encontradas diferenças significativas na capacidade vital forçada

(CVF) e no volume expiratório forçado no primeiro segundo (VEF1)10. Por outro lado,

vários indivíduos saudáveis começam a apresentar diminuição da função pulmonar

somente a partir dos 30 anos de idade11. Além disso, a força muscular respiratória é

prejudicada pelo envelhecimento, sendo verificadas reduções entre 8-10% a cada

década, após a idade de 40 anos12;13. Similarmente, Janssens10 observou redução

da força do diafragma em idosos quando comparados à força do diafragma em

indivíduos jovens.

Apesar das melhores condições e aumento da expectativa de vida e

do adiamento do aparecimento das limitações, deficiências e agravos à saúde em

indivíduos idosos, evidências apontam um aumento no número de doenças crônico-

degenerativas neste grupo2;14-19. É comum indivíduos idosos conviverem

frequentemente com os problemas crônicos de saúde, com consequente elevado

consumo de medicamentos20-26.

Uma classe de fármacos amplamente prescrita atualmente são os

inibidores da enzima conversora de angiotensina (IECA)27. Utilizados primariamente

na terapia anti-hipertensiva27-29, desempenham importante papel no tratamento da

14

insuficiência cardíaca30-32, nefropatia diabética e não diabética33;34, hipertrofia

ventricular35, doença coronariana36 e em pacientes que se submeteram a

transplante renal33;37.

Os IECA podem promover efeitos benéficos no sistema músculo-

esquelético38. Há evidências que estas drogas melhoram a massa e a força

muscular30;39;40. Uma vez que os IECA podem melhorar a força dos músculos

esqueléticos38;39;41, postula-se que o mesmo efeito poderia ser observado nos

músculos respiratórios. Entretanto, poucos estudos estão disponíveis na literatura

acerca desta temática42;43.

Considerando que o declínio da função pulmonar e da força

muscular respiratória podem aumentar a mortalidade44;45, a busca de estratégias

para prevenir ou reduzir esse declínio é importante para a promoção de saúde

deste grupo populacional.

Há evidências que o treinamento físico pode reduzir o declínio da

força muscular respiratória e a função pulmonar em diversas populações, inclusive

em reduções relacionadas ao envelhecimento46-49. Entretanto, essa abordagem

possui limitações relacionadas à baixa adesão dos participantes39;50.

São raros os relatos de intervenções farmacológicas capazes de

auxiliar na prevenção do declínio da capacidade física40, da força muscular

respiratória e da função pulmonar em idosos43. Contudo, tal hipótese apresentaria

importantes implicações na saúde pública para esta população, possibilitando-os

uma melhor qualidade de vida, maior expectativa de vida e menores índices de

mortalidade. Desta forma, este trabalho objetivou verificar os efeitos do uso crônico

de IECA sobre a força muscular respiratória e a função pulmonar de idosos

fisicamente independentes.

15

2 REVISÃO DE LITERATURA – CONTEXTUALIZAÇÃO

2.1 PROCESSO DE ENVELHECIMENTO

O envelhecimento populacional é um evento incontestável

mundialmente, uma vez que se observa um aumento considerável da população

idosa em relação aos demais grupos etários em todo o mundo1-3.

Envelhecimento e senescência são palavras relacionadas e são

muitas vezes usadas como sinônimos. Ambos processos são caracterizados por

mudanças progressivas no tecido do corpo, o que leva a um declínio na função e

morte do organismo. Senescência se refere a um processo de pós-maturação que

leva à diminuição da homeostase e maior vulnerabilidade do organismo à morte.

Envelhecimento, em contrapartida, refere-se a qualquer processo relacionado com o

tempo, sendo um processo contínuo que começa na concepção e continua até a

morte51;52. Contudo o envelhecimento geralmente é compreendido como declínio

progressivo na homeostase após a fase reprodutiva da vida, resultando em aumento

do risco de doença ou morte11;53. Os mecanismos envolvidos no envelhecimento

são parcialmente intrínsecos ao organismo, como fatores genéticos e epigenéticos,

e extrínsecos, tais como nutrição, exposição à radiação e estresse51.

O aumento da expectativa de vida nas populações humanas em

todo o mundo é um triunfo da pesquisa biomédica. O ganho extraordinário de cerca

de 30 anos na expectativa de vida na Europa Ocidental, nos EUA, Canadá, Austrália

e Nova Zelândia e ganhos ainda maiores no Japão e alguns países da Europa

Ocidental, como Espanha e Itália, destaca-se como uma das realizações mais

importantes do século 202. Tal aumento deve-se às menores taxas de fecundidade4,

melhorias na saúde pública, imunização e antibioticoterapia, e também por causa de

outras melhorias no estilo de vida tais como uma melhor habitação1.

No Brasil, o ritmo de crescimento da população idosa tem sido

sistemático e consistente. Segundo a Pesquisa Nacional por Amostra de Domicílios

– PNAD, realizada em 2009, o país contava com uma população de cerca de 21

milhões de pessoas de 60 anos ou mais de idade4.

Outro indicador que mostra o processo de envelhecimento da

população brasileira é o índice de envelhecimento. Em 2008, para cada grupo de

100 crianças de 0 a 14 anos, havia 24,7 idosos de 65 anos ou mais de idade. Entre

16

2035 e 2040, estima-se que a população idosa seja superior à de crianças, em

2050, a relação poderá ser de 100 para 172,754.

O envelhecimento da população brasileira se dará,

necessariamente, a ritmo maior do que aquele ocorrido nos países do Primeiro

Mundo, principalmente naqueles que iniciaram sua transição da fecundidade ainda

no século XIX. Por outro lado, esses países, antes do início do processo, já

conviviam com populações menos jovens, por nunca terem experimentado níveis

tão altos de fecundidade quanto o Brasil55.

Estudos mostram que o número de pessoas idosas cresce em ritmo

maior do que o número de pessoas que nascem acarretando um conjunto de

situações que modificam a estrutura de gastos dos países em uma série de áreas

importantes4.

Com uma taxa de fecundidade abaixo do nível de reposição

populacional, combinada ainda com outros fatores, tais como os avanços da

tecnologia, especialmente na área da saúde, atualmente o grupo de idosos ocupa

um espaço significativo na sociedade brasileira4.

2.2 ENVELHECIMENTO DO SISTEMA RESPIRATÓRIO

O processo de envelhecimento afeta cada célula, tecido e órgão. As

alterações são decorrentes de uma combinação de fatores, genética, meio

ambiente, aspectos nutricionais e estilo de vida5-7.

O sistema respiratório sofre modificações anátomo-funcionais

inerentes ao processo de envelhecimento, embora possam variar de amplitude5. As

mudanças que ocorrem a este nível são clinicamente relevantes porque a

deterioração da função pulmonar está associada a um aumento da taxa de

mortalidade. Neste contexto, o conhecimento das mesmas contribui para a detecção

e prevenção de disfunções respiratórias em idosos9.

As alterações do sistema respiratório podem ser explicadas pelos

seguintes fatores: alteração no recolhimento elástico do pulmão; diminuição

progressiva da complacência da parede torácica; diminuição da força muscular

respiratória e mudança da resposta à hipóxia e hipercapnia56;57.

17

Existe diminuição no recolhimento elástico pulmonar, devido a

redução do número de fibras elásticas nos pulmões em idosos5. Essa alteração

resulta em aumento da complacência pulmonar, que é uma característica do pulmão

senil. Por outro lado, a diminuição do recolhimento elástico do pulmão favorece o

fechamento prematuro das vias aéreas, resultando em redução tanto da ventilação

perfusão (V/Q) quanto nos fluxos expiratórios56.

A perda de elasticidade do pulmão poderia explicar as mudanças no

VEF1 e na CVF, através da redução da pressão para o fluxo expiratório máximo.

Além disso, a troca gasosa também é comprometida, com uma resposta reduzida à

hipóxia e hipercapnia58.

As principais alterações fisiológicas do processo de envelhecimento

relacionada com a caixa torácica consistem em uma diminuição da distensão

dinâmica5, que está associada com a calcificação das cartilagens costais e junções

condroesternais, das articulações costo-vertebrais, além da perda de altura

vertebral, resultando em um aumento no diâmetro anterior-posterior do tórax,

enquanto ocorrem declínio na função dos músculos respiratórios58.

Estenne e cols.59 avaliaram as mudanças no tamanho da caixa

torácica relacionadas com a idade em 50 indivíduos saudáveis, com idade entre 24-

75 anos. Neste estudo, o envelhecimento foi associado com uma diminuição

significativa (31%) na complacência da parede torácica, envolvendo a caixa

torácica, as costelas e o diafragma.

A força muscular respiratória é prejudicada pelo envelhecimento,

sendo verificadas reduções entre 8-10% a cada década, após a idade de 40

anos12;13. Neste contexto, Janssens e cols.10 observaram redução da força do

diafragma em idosos quando comparados à força do diafragma em indivíduos

jovens.

Tais modificações relacionadas ao envelhecimento ocorrem

principalmente devido as mudanças geométricas da caixa torácica, pela diminuição

da complacência da parede torácica e pelo aumento da capacidade residual

funcional (CRF), resultante da diminuição da retração elástica do pulmão10 e pela

sarcopenia relacionada ao envelhecimento12. Além disso, observa-se diminuição no

tamanho, no número de fibras musculares e na capacidade da junção

neuromuscular de transmitir impulsos nervosos, a perda de neurônios motores

18

periféricos e redução da capacidade de trabalho muscular, que juntos pode reduzir a

força muscular5;10.

Existe uma diminuição acentuada nas respostas ventilatórias à

hipóxia e hipercapnia em idosos6;56. Kronenberg e Dragecom60 compararam as

respostas à hipercapnia e hipóxia em jovens saudáveis (22-30 anos) com os de

homens mais velhos (64-73 anos). Nos indivíduos mais velhos, a resposta

ventilatória à hipóxia foi quatro vezes menor do que o grupo mais jovem e a

resposta à hipercapnia foi reduzida em 58%.

A função pulmonar sofre alterações decorrentes do envelhecimento,

apresentando deterioração das medidas estáticas e dinâmicas5;7-9, sendo que, até a

idade de 25 anos, não são encontradas diferenças significativas na CVF e no

VEF110. Vários indivíduos saudáveis começam a apresentar diminuição da função

pulmonar a partir dos 30 anos de idade11.

A capacidade vital forçada (CVF), medida que representa o volume

máximo de ar exalado com esforço máximo, a partir do ponto de máxima

expiração61,62, é o teste de função pulmonar mais importante, porque num dado

indivíduo, durante a expiração, existe um limite para o fluxo máximo que pode ser

atingido em qualquer volume pulmonar, sendo essencial para diagnosticar

obstrução ao fluxo aéreo e para descartar um processo restritivo63. Os valores

máximos da CVF são alcançados em torno de 25 anos no sexo masculino, e 20

anos no sexo feminino56, podendo permanecer inalterados até os 35-40 anos,

seguindo-se por uma fase de declínio que se acelera após os 55 anos63.

O volume expiratório forçado ao primeiro segundo (VEF1)

representa o volume de ar exalado no primeiro segundo da manobra de CVF63.

Usado basicamente para avaliar distúrbios obstrutivos, diminui claramente a uma

taxa que depende da idade e do gênero58, apresentando um declínio a partir da

terceira década de vida, a uma taxa aproximadamente de 26ml/ano para homens e

20 ml/ano para as mulheres8.

Estudos transversais e longitudinais mostram um declínio

acelerado, mas não linear da CVF e do VEF1 com a idade, sendo que a taxa de

declínio é maior em homens do que em mulheres e mais rápida em pacientes que

têm maior reatividade das vias aéreas10.

19

Uma vez que ocorre uma queda do CVF e da VEF1 relacionadas

com o envelhecimento, uma consequente redução na razão entre o VEF1 e a CVF

(VEF1/CVF) é esperada9. Essa relação, conhecida como índice de Tiffeneau, é

amplamente usada para definir a presença de doença obstrutiva das vias aéreas64.

Apresenta diminuição de 75% para 70% aos 70 anos de idade58. Deve-se observar

que diretrizes usam uma razão VEF1/CVF de 70% como valor limite para

diagnóstico de limitação do fluxo aéreo65.

2.3 DOENÇAS CRÔNICO-DEGENERATIVAS E CONSUMO DE MEDICAMENTOS EM IDOSOS

Apesar das melhores condições e aumento da expectativa de vida e

do adiamento do aparecimento das limitações, deficiências e agravos à saúde em

indivíduos com idade superior a 65 anos, evidências apontam um aumento no

número de doenças crônicas e condições neste grupo etário2;14-19.

Esse aumento na prevalência de doenças crônicas, incluindo

doenças cardíacas, artrite e diabetes, foi observado em idosos entre 1980 e 1990

nos EUA66-68, nos países da Organização para Cooperação e Desenvolvimento

Econômico69, nos Países Baixos15, no Reino Unido70 e na Suiça71.

Com o crescimento demográfico da população brasileira acima de

60 anos, estabelecem-se alterações nos padrões de saúde, com a redução da

morbidade e mortalidade por doenças infecciosas, paralelamente ao aumento da

prevalência de doenças crônicas não transmissíveis72.

No Brasil, apenas 22,6% das pessoas de 60 anos ou mais de idade

declararam não possuir doenças. Para aqueles de 75 anos ou mais de idade, esta

proporção cai para 19,7%4. Além disso, cerca de 72% das mortes foram atribuídas

as doenças crônicas, incluindo doenças cardiovasculares, respiratórias, diabetes,

câncer, doenças renais e outras73.

Além disso, verifica-se no território brasileiro que quase metade

(48,9%) dos idosos sofria de mais de uma doença crônica e, no subgrupo de 75

anos ou mais de idade, a proporção atingia mais da metade (54,0%). Entre as

doenças crônicas, a hipertensão é a que mais se destaca em todos os subgrupos de

idosos, com proporções em torno de 50%. Doenças como artrite ou reumatismo

20

aparecem, também, com bastante frequência entre as pessoas de 60 anos ou mais

de idade: 35,1% e 24,2%, respectivamente4.

Neste contexto, observamos que indivíduos idosos convivem

frequentemente com os problemas crônicos de saúde, com consequente elevado

consumo de medicamentos20-26.

Nos últimos anos, o número de medicamentos prescritos tem

aumentado progressivamente em todo o mundo20;74, e os idosos são os principais

consumidores de drogas20;75.

Uma classe de fármacos amplamente prescrita atualmente são os

inibidores da enzima conversora de angiotensina (IECA)27. Utilizados primariamente

na terapia anti-hipertensiva27-29, desempenham importante papel na prevenção de

várias complicações relacionadas ao envelhecimento76. Apresentam benefícios

comprovados quando à redução da mortalidade31, menores taxas de

incapacidade39, morbidade e internações hospitalares41.

2.4 INIBIDORES DA ENZIMA CONVERSORA DE ANGIOTENSINA (IECA)

2.4.1 Classificação e Mecanismo de Ação

Descrita pela primeira vez na década de 6077;78, esta classe de

drogas demonstrou ser muito eficaz no tratamento da hipertensão arterial,

apresentando como principais representantes o captopril, ramipril, enalapril,

fosinopril, lisinopril e quinapril79.

Os inibidores da ECA (IECA) podem ser classificados em três

grupos: (1) grupo formado pelo radical sulfidril, composto basicamente pelo

captopril; (2) grupo formado pelo radical carboxil, composto pela maioria das

substâncias: como o enalapril, lisinopril, benazepril, quinapril, ramipril, entre outros;

(3) grupo formado pelo radical fosforil, composto pelo fosinopril80. Uma série de

IECA foram lançados no mercado e vêm sendo utilizados na prática médica81.

O sistema renina-angiotensina-aldosterona (SRAA) é importante na

regulação da homeostase fisiológica central e na regulação da pressão arterial,

estando diretamente relacionado com a hipertensão arterial82;83.

21

A renina, primeira enzima do SRAA clássico, é produzida nas

células justaglomerulares da arteríola aferente renal, sintetizada e armazenada sob

a forma inativa chamada pró-renina. A pró-renina é processada no retículo

endoplasmático então e armazenada em grânulos secretores pelo aparelho de

Golgi, onde uma parte parece ser convertida em renina ativa. Tanto a pró-renina

quanto a renina são principalmente liberadas após a estimulação das células justa-

glomerulares renais84;85.

Quando a renina plasmática reage através de clivagem com seu

substrato, o angiotensinogênio, uma α globulina produzida principalmente pelo

fígado86, ocorre a formação da angiotensina I, um decapeptídeo com propriedades

vasoconstritoras moderadas, mas não suficientes para causar alterações

significativas da função circulatória87.

A angiotensina I é convertida para a forma fisiologicamente ativa,

em angiotensina II, pela ação da dipeptidil carboxipeptidase ou enzima conversora

de angiotensina (ECA)83,88, a qual origina-se a partir células endoteliais42, é

abundantemente encontrada em diversos tecidos orgânicos, incluindo o endotélio

dos vasos pulmonares e no músculo esquelético 89-91, sendo um contribuinte

importante para a homeostasia cardiovascular92.

A angiotensina II é um octapeptídeo vasoativo, considerado o

principal mediador do sistema renina-angiotensina-aldosterona, que modula a

resistência vascular através da ligação aos receptores endoteliais causando

vasoconstrição e aumento da pressão arterial, e regula o equilíbrio hidroeletrolítico

por efeito indireto sobre a aldosterona que, por sua vez, estimula a retenção de sal e

água, mecanismos que contribuem para o aumento da pressão arterial84.

Além do seu efeito sobre a gênese de angiotensina II, a ECA

também atua na degradação da bradicinina. A bradicinina pertence ao grupo das

cininas, que são polipeptídeos sintetizados no plasma e/ou líquido intersticial, a

partir de proteínas de elevado peso molecular, envolvidos em diversos eventos

biológicos, incluindo aumento da permeabilidade vascular, relaxamento da

musculatura lisa e vasodilatação93. A ação farmacológica da bradicinina na

regulação da pressão arterial envolve vasodilatação, redução da resistência

vascular periférica, regulação da excreção de sódio nos rins94. Dessa forma, após

tratamento com IECA ocorre aumento nos níveis circulantes de bradicinina, com

posterior liberação de prostaglandinas, prostaciclinas e óxido nítrico (NO), causando

22

natriurese, redução da pressão arterial, oferecendo efeito adicional cardioprotetor

desempenhado pelos IECA95. Ou seja, os efeitos cardiovasculares benéficos

produzidos pelos IECA não se devem apenas à redução na síntese de angiotensina

II, mas também à potenciação dos efeitos biológicos da bradicinina, devido sua

menor degradação endógena93.

Os efeitos benéficos decorrentes do aumento nos níveis circulantes

de bradicinina não são observados nos bloqueadores dos receptores da

angiotensina II (BRA), pois estes agindo diretamente no receptor AT1 não bloqueiam

a ECA94.

2.4.2 Efeitos Farmacológicos e Indicação Clínica

Aplicados no tratamento e prevenção de diversas doenças98, os

IECA apresentam efeitos benéficos no tratamento da hipertensão arterial33;99,

insuficiência cardíaca30-32, nefropatia diabética e não diabética33;34, hipertrofia

ventricular35, doença coronariana36;100 e em pacientes que se submeteram a

transplante renal33;37.

O uso de IECA pode aumentar a sensibilidade do reflexo de tosse,

particularmente em idosos, melhorando o reflexo da deglutição76, dessa forma

reduzindo a mortalidade por pneumonia, quando comparado com idosos tratados

com outros anti-hipertensivos. O mesmo autor relata ainda que o uso de IECA pode

retardar o declínio cognitivo em pacientes com doença leve a moderada de

Alzheimer.

Além disso, o uso de IECA parece estar relacionado com o

aumento da densidade mineral óssea entre os idosos101. Foi realizado estudo

transversal em 3.887 chineses idosos. Após análises de regressão múltipla, o uso

de IECA foi associado com maior densidade mineral óssea do colo do fêmur nas

mulheres, total de quadril e da coluna lombar em homens.

O tratamento com IECA também melhora o balanço autonômico em

ratos idosos102 , a sensibilidade baroreflexa em humanos103, em indivíduos com

disfunção ventricular104, diminuindo a atividade simpática central105.

23

Em relação as alterações metabólicas, melhoram a sensibilidade à

insulina106-108 e são capazes de reduzir a gordura corporal, sem alterar o perfil

lipídico sérico109.

Os IECA reduzem a morbidade, mortalidade, número de admissões

hospitalares e declínio da capacidade funcional em pacientes com insuficiência

cardíaca congestiva41;110.

2.4.3 Efeito dos IECA na Força Muscular Respiratória e Função Pulmonar

Uma vez que os IECA podem melhorar a força dos músculos

esqueléticos38;39;41, o mesmo benefício pode igualmente influenciar os músculos

respiratórios42. Entretanto, poucos estudos estão disponíveis na literatura acerca

desta temática.

Estudo43 avaliou 18 pacientes com insuficiência cardíaca crônica

estável, tratados com perindropil por 06 meses. Após esse período, notou-se um

aumento significativo na PImax e na PEmax. Em relação ao valor basal, os pacientes

com insuficiência cardíaca crônica apresentaram uma melhora de 21% em seus

valores absolutos de PImax após a terapia de longo prazo com perindopril enquanto

PEmax melhorou em cerca de 10% nestes pacientes. Tal estudo fornece a primeira

evidência de que a fraqueza muscular respiratória em pacientes com insuficiência

cardíaca crônica poderia ser parcialmente reversível com o tratamento com IECA.

Entretanto, no mesmo estudo, não foi encontrado diferenças significativas na função

pulmonar, avaliada através dos índices CVF, VEF1 e VEF1/CVF. Outro estudo42

observou que a redução nos níveis plasmáticos da ECA circulante estava

relacionada com maior força muscular respiratória, avaliada através da PImax, em

recém-nascidos.

O comprometimento da força muscular respiratória tem sido

estudado extensivamente em indivíduos portadores de doenças cardíacas,

pulmonares e neuromusculares. Reconhecidamente, é um contribuinte para o

aparecimento de insuficiência ventilatória e mortalidade nestas condições111 .

Entretanto, pesquisadores44 sugerem que a força muscular

respiratória está situada no início de uma cadeia causal, que pode levar a

diminuição da função pulmonar e morte. Estes resultados ressaltam a importância

24

de manter a força dos músculos respiratórios em idosos e da necessidade de

intervenções objetivando melhorar a força muscular respiratória e função pulmonar,

na tentativa de reduzir a mortalidade nesse grupo populacional.

Sabe-se que a função pulmonar está amplamente reduzida em

idosos56;57;112 . Sabendo que a falta de declínio na CVF poderia refletir numa melhor

condição muscular e maior força respiratória63 e que uma maior função pulmonar

confere vantagem de sobrevida63;113, a pesquisa de meios que melhorem estes

parâmetros são relevantes.

Poucos estudos sugerem que o uso de medicamentos possa

favorecer a função pulmonar. Entretanto, o uso de IECA tem sido associado com um

risco reduzido de pneumonia, por melhora da tosse e deglutição98,114, uma vez que

indivíduos idosos e debilitados, nos quais a aspiração silenciosa é considerada uma

importante causa de pneumonia, a melhora da deglutição e da tosse são

considerados fatores importantes para prevenção de infecções pulmonares. A

terapia com IECA também pode ser indicada para prevenção das exacerbações da

doença pulmonar obstrutiva crônica (DPOC), em indivíduos com reflexos de

deglutição prejudicados115.

Em 2006, pesquisadores116 avaliaram a terapia a longo prazo com

peridronpil, um inibidor da ECA, em pacientes portadores de DPOC e cor pulmonale

crônico. Foram avaliados 40 pacientes, com idade média 45 ± 2 anos. Houve

melhora nos parâmetros hemodinâmicos, na hipertensão pulmonar e na função

pulmonar.

Outro estudo29 verificou que o uso do captopril, um IECA, reduziu

drasticamente a lesão pulmonar induzido pelo ácido oléico em ratos, diminuindo o

edema intersticial, hemorragia e a infiltração celular, além de melhorar a oxigenação

do sangue nos ratos. Além disso, pesquisadores117,118 demonstraram que a inibição

da ECA restaura a permeabilidade alvéolo-capilar em pacientes com insuficiência

cardíaca congestiva.

Aumentos significativos na performance, medida através do VO2

submáximo, foram observados em portadores de insuficiência cardíaca congestiva,

usuários de IECA119. O nível de VO2 submáximo aumentou cerca de 15% para o

uso de um IECA, chegando a aumentos de 26% quando foram utilizados dois

medicamentos desta classe combinados. A melhora nesses índices é atribuída à

melhora da função pulmonar, causada pelo uso de IECA, melhorando o trabalho

25

aeróbico92. Resultado similar foi apresentado por Pascual e cols.45 que relataram

que uma combinação de dois agentes da classe IECA resultou em aumento de

4,7% no VO2 submáximo, em pacientes com disfunção sistólica do ventrículo

esquerdo.

Níveis plasmáticos da ECA e da angiotensina II estariam

relacionados com uma pequena variação na função pulmonar ou no pico de VO2.

Estudos sugerem uma melhora significativa na capacidade do exercício em usuários

de altas doses de IECA, quando comparado com o uso destes agentes em doses

mais baixa114, demonstrando influência clara dos níveis plasmáticos da ECA nesses

parâmetros analisados.

Entretanto, há estudos que apontam resultados controversos. O uso

de IECA não está associado com nenhuma mudança mensurável na função

pulmonar, inclusive no VEF1, em pacientes com obstrução crônica do fluxo

aéreo120,121 ou em pacientes asmáticos122.

Considerando que o declínio da função pulmonar e/ou da força

muscular respiratória pode aumentar a mortalidade44;63, a busca de estratégias para

prevenir ou reduzir a velocidade com que esse declínio se estabeleça em idosos

são importantes estratégias para a promoção de saúde deste grupo populacional.

Há evidências que o treinamento físico pode reduzir o declínio da

força muscular respiratória e a função pulmonar em diversas populações, inclusive

em reduções relacionadas ao envelhecimento46-49. Entretanto, estes treinos

possuem limitações relacionadas à baixa adesão dos participantes39;50.

São raros os relatos de intervenções farmacológicas capazes de

auxiliar na prevenção do declínio da capacidade física40, da força muscular

respiratória e da função pulmonar em idosos43. Contudo, tal hipótese apresentaria

importantes implicações na saúde pública para esta população, possibilitando-os

uma melhor qualidade de vida, maior expectativa de vida e menores índices de

mortalidade. Desta forma, este trabalho objetivou verificar os efeitos do uso crônico

de IECA sobre a força muscular respiratória e a função pulmonar de idosos

fisicamente independentes.

26

3. ARTIGO

ANÁLISE DA FUNÇÃO RESPIRATÓRIA DE IDOSOS FISICAMENTE

INDEPENDENTES USUÁRIOS DE INIBIDORES DA ENZIMA CONVERSORA DE

ANGIOTENSINA (IECA) (A ser submetido ao periódico Journal of the American

Geriatrics Society - Qualis A1 )

Santos, Denis C.1,2; Freitas, Eliane R.F.S.1; Araujo, Evelize C. L. S.1;; Coelho,

Vinícius A. 1,2; Pelosi, Gislaine G.3, Fernandes, Karen B.P.1,2.

1Centro de Pesquisa em Ciências da Saúde (CPCS), Centro de Ciências Biológicas

e da Saúde (CCBS), Universidade Norte do Paraná (UNOPAR), Londrina, PR.

2Programa de Mestrado associado UEL/UNOPAR em Ciências da Reabilitação,

Londrina, PR.

3 Centro de Ciências Biológicas, Departamento de Farmacologia, Universidade

Estadual de Londrina (UEL).

Corresponding Author:

Karen Barros Parron Fernandes

Centro de Pesquisa em Ciências da Saúde, Universidade Norte do Paraná.

Av. Paris, 675, Jardim Piza, Londrina/PR/Brasil,

CEP 86041-140 - Caixa Postal: 401,

Fone: 55 43 3371-7990.

E-mail: [email protected]

RUNNING TITLE: Angiotensin Converting Enzyme Inhibitors And Pulmonary Function.

27

ABSTRACT

Objectives: The aim of this study was to investigate the effects of long-term ACEI therapy on respiratory function in physically independent elderly. Design: For this retrospective cross-sectional study, patients were randomly selected from an ageing study (EELO project) performed in Londrina, Brazil. The selected subjects were grouped into three categories according to the medication usage: I) patients using ACEI for at least six months were referred as experimental group (ACEIG), II) elder patients with normal pulmonary function, referred as control group (CG) and III) Angiotensin-II Receptor Blockers (ARBG). Respiratory muscle strength was assessed by measuring maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) using manovacuometer while pulmonary function was evaluated by spirometry (considering the following variables: FVC, FEV1, FEV1/FVC ratio). All the variables were presented as % of predicted values, corrected for Brazilian population. Results: ACEIG (102.2%) and ARBG (109.7%) showed higher values for MIP when compared to control group (CG: 93.2%), according to Kruskall-Walis’ test (p=0.001). Similar results were observed considering the MEP (ACEIG: 119.9%pred.; ARBG: 103.7%pred.; CG:103.1%pred, p=0.003). Moreover, the ACEIG showed higher FVC (ACEIG: 92.47%pred.; CG: 86.65%pred.; ARBG: 87.87%pred.; p=0.010), higher FEV1(ACEIG: 97%pred.; CG: 90.5%pred.; ARBG: 83.25%pred., p=0.001) and higher FEV1/FVC (ACEIG: 106%; CG: 102%; ARBG:106.5%, p=0.003) than control group. However, the ARBG was similar to ACEIG and CG regarding lung function. Conclusion: According to these results, ACEI therapy seems to be related with better respiratory muscle strength and pulmonary function in physically independent elderly. Key words: Angiotensin-Converting Enzyme Inhibitors. Respiratory Muscle Strength. Pulmonary Function. Elderly.

28

INTRODUCTION

A significant increase in life expectancy is found worldwide recently,

with consequent growth of the elder population, compared to other age groups. The

aging process besides complex affects all organs and cells1.

The respiratory system undergoes aging-related anatomical and

functional changes. However, these changes may vary substantially among different

individuals2. Similarly, lung function is also affected with deterioration of both static

and dynamic measurements2. In addition, respiratory muscle strength is impaired by

aging, and it has been observed reductions of 8-10% per decade after 40 years3.

Despite better conditions and increased life expectancy in older

adults, evidences show an increase in chronic degenerative diseases in this group1;4.

Thus, elder people often live with chronic health problems, with consequent high

drug’s consumption5.

Angiotensin-Converting Enzyme Inhibitors (ACEI) are drugs widely

used by seniors. Although they are mainly recommended for antihypertensive

therapy6, they also play an important role in the treatment of heart failure7, diabetic

and non-diabetic nephropathy8, ventricular hypertrophy9 and coronary disease10.

Moreover, the Angiotensin-II Receptor Blockers (ARB) is another

drug class with similar pharmacological effects than ACEI, once these drugs prevent

the binding of angiotensin II to its receptor. However, ARB do not seem to interfere

in circulating levels of bradykinin, as ACEI, since Angiotensin Converting Enzyme

(ACE) is also involved in bradikinin degradation11.

ACEI may promote beneficial effects on skeletal muscles12. There is

evidence that these drugs can improve the mass and muscle strength7;13;14.

29

Whereas ACEI can improve muscle strength12;13;15 it may be postulated that the

same pharmacological effect could also influence the respiratory muscles.

Considering that the decline in lung function and respiratory muscle

strength may increase mortality16, strategies to prevent or reduce the speed of such

decline in elderly may be important for health promotion of this population group,

once it may evoke a better quality of life, higher life expectancy and lower mortality

rates. Exercise training can reduce the decline in respiratory muscle strength and

pulmonary function in several populations even in elder subjects17. However, these

programs have limitations related to poor adherence of individuals13;18.

There are few reports of pharmacological interventions which can

help preventing the physical decline14, and respiratory muscle strength or pulmonary

function in older adults19. However, few studies are available in the literature about

this subject19;20. Additionally, there are no studies comparing the effects of ACEI with

ARB on physical performance.

Thus, this study aimed to determine the effects of chronic use of

ACEI or ARB on the respiratory muscle strength and pulmonary function in physically

independent elderly.

30

SUBJECTS AND METHODS

ETHICAL PROCEDURES

This study was approved by the Research Ethics Committee

from the university (protocol no. PP0063/09, Appendix B). Patients received

information about the nature of the study and signed the informed consent prior to

any methodological procedure.

DESIGN AND ELEGIBILITY CRITERIA FOR THE POPULATION STUDY

This cross-sectional study followed the criteria established by

Strengthening the Reporting of Observational Studies in Epidemiology – STROBE21.

The convenience sample consisted of older adults (age over 60, according to

recommendations of World Health Organization for developing countries22) who

participated on an interdisciplinary project (EELO Project - Study on Ageing and

Longevity). The EELO Project is a thematic project developed at University of

Northern Parana (UNOPAR) which aimed to evaluate the socio-demographic factors

and indicators of health conditions of older adults in Londrina, a city of Northern

Paraná, Brazil. Information can be found at http://www2.unopar.br/sites/eelo/. This

study was developed in Londrina as the elder population of this city represents 12%

of the total population, which is similar to what has been described in other

countries23;24. The total sample of the EELO project consisted of 508 individuals,

which is representative of the 43610 citizens older than 60 years living in Londrina.

Of those, 256 individuals did not undergo at least one of the tests used in the

analysis of our study and could not be included in the sample. Therefore, the

convenience sample of the present study consisted of 252 physically independent

31

elderly according to the classification proposed by the Functional Status Spirduso

(levels 3 and 4). This means that older adults are able to perform basic activities of

daily life and also the instrumental activities of daily life. The individuals from level 3

have low exercise capacity and are sedentary, and individuals from level 4 have

exercise capacity above average and are considered as physically active25.

Inclusion criteria

Individuals using Angiotensin-Converting Enzime Inhibitors for at

least six months were included at the experimental group (ACEIG). The control

group (CG) was composed by elderly with normal pulmonary function. In order to

evaluate if changes observed were evoked by angiontensin synthesis and not only to

a blockage of angiontensin-II receptor, another group of individuals who were using

Angiontensin-II Receptor Blockers (ARBG) were included and designed as positive

control group.

Exclusion criteria

Pulmonary diseases, thorax abnormalities, ventilatory disorders

according to criteria established by Pereira26 and recommended by Brazilian Society

of Pneumology and Tisiology, smoking history, cardiac insufficiency and the usage of

pills for that, respiratory infection over the last 30 days and previous or actual

smoking habit were established as the exclusion criteria for this research. After

analysis of inclusion/exclusion criteria, 252 individuals were included.

32

DATA COLLECTION

Co-morbidity and medication questionnaires

There were collected data about the presence of co-morbidities and

medication consumption using structured questionnaires. Additionally, questions

concerning height and weight were also included in order to determinate

anthropometric characteristics.

Respiratory muscle strength evaluation

The patients’ respiratory muscle strength was evaluated through the

measure of the maximal inspiratory pressure (MIP) and maximal expiratory pressure

(MEP) using the GERAR® analog manovacuometer (GERAR®, São Paulo, Brazil)

featuring a -200 to + 200 cmH2O scale, a capsule type sensor and a spigot

connection. The exams for data collection attended international standards

established by the American Thoracic Society27, previously described by Black and

Hyatt28. There were performed at least 3 maneuvers, being 2 reproducible

(difference lower than 10% between values).

The highest value of respiratory muscle strength (MIP and MEP)

found was used and it was expressed in percentage of predicted values described

for Brazilian population, according to the Neder et al.3.

Pulmonary function test

Pulmonary variables including forced vital capacity (FVC), forced

expired volume at the first second (FEV1), FEV1/FVC ratio were measured by Pony-

FX spirometer (COSMED, SRL, Rome, Italy).The exams attended international

33

standards established by the American Thoracic Society and the European

Respiratory Society29.

Spirometry was performed at controlled temperature room. The

subjects took a rest from 5 to 10 minutes before the test and during this period, they

remained sitted and using a nose clip. Before the procedure started, it was carefully

described. The spirometer was computerized and printed the FEV1 and FVC values

after the forced expiration had been performed. Best of three satisfactory readings

was taken for the analysis whereas the two greater values of FEV1 and FVC should

differ less than 0.15 L30. The highest value for FVC and FEV1 were used in the ratio

FEV1/FVC. The variables were shown as the percent predicted values based on

regression equations for Brazilian population26. Individuals whose spirometric values

were lower than the value established for Brazilian population were excluded from

the sample (figure 1).

STATISTICAL ANALYSIS

Statistical analysis was performed using GraphPad Prism 5.0 and

Bioestat 5.0., setting the confidence interval in 95% and 5% of the significance level

(p<0,05) for all tests.

Chi Square’s test was used to compare the gender distribution

among groups. Additionally, one way ANOVA was used to compare age and

antropometric data (weight, height and body mass índex) between the groups.

After data collection, Shapiro-Wilk’s test was used to evaluate

whether the data had normal distribution. Considering that the variables used did not

show normal distribution, all data were presented as median and interquartile

intervals (1st.Q-3rd.Q.).

34

Kruskall-Walis’ test was used to compare the groups concerning the

variables related to muscle respiratory strenght (MIP and MEP) and pulmonary

function (FVC, FEV1, FEV1/ FVC), followed by Dunn’s test.

35

RESULTS

PILOT STUDY AND SAMPLE SIZE CALCULATION

A pilot study was performed to calculate the minimum sample size

required to test the null hypothesis that there is no difference between the MIP and

MEP and lung function between the experimental and control groups. For this, the

values of MIP (GE: 110.4 ± 28.1 cmH20 versus CG: 86.9 ± 15.2 cmH20) and MEP

(GE: 114.4 ± 30.1 versus cmH20 GC: 94. 42 ± 22.2 cmH20) from the pilot study were

considered and it was also established the following statistical parameters: Power of

test: 0.9 and p <0.05. Therefore, it was stated a minimum sample of 30 subjects for

the experimental and 61 individuals for the control group.

SUBJECTS

Initially, the study was composed of 468 individuals. However, 252

met the eligibility criteria and comprised the final sample: 150 patients at the control

group (CG), 80 patients at the ACEI group (ACEIG) and 22 patients at the positive

control group (ARBG). 216 elderly people were excluded because they had at least

one of the following exclusion criteria: respiratory diseases (asthma or CPOD),

pulmonary function disorders (restrictive or obstructive), smoking history (with or

without impairment of lung function) or heart failure. Figure 1 shows a flowchart of all

recruited individuals.

All groups had similar demographic (gender, age) and

anthropometric data (weight, height, body mass index), being these data shown in

table 1 (p> 0.05). Therefore, it may be assumed that the groups were matched for

age, gender and anthropometric status.

36

RESPIRATORY MUSCLE STRENGTH

The inspiratory muscle strength (assessed by MIP) was higher in

users of ACEI (ACEIG) and ARB (ARBG), when compared with individuals non-

users of this medication (CG). However, inspiratory muscle strength was similar

between the ACEI and ARBG (table 2).

Similarly, expiratory muscle strength (assessed by MEP) was higher

in users of ACEI (ACEIG) and ARB (ARBG) when compared with individuals non-

users of this medication (CG). However, expiratory muscle strength was similar

between the ACEI and ARBG (table 2).

PULMONARY FUNCTION

The FVC was higher in users of ACEI (ACEIG) when compared with

patients from control group (Table 3). However, no differences were observed

among users of ACEI (ACEIG) and ARB users (ARBG). Additionally, no difference

was observed between users of ARB (ARBG) and control individuals (Table 3).

Considering the FEV1, significant difference was observed between

ACEIG and control group (Table 3). However, no differences were observed among

users of ACE inhibitors (ACEIG) and ARB users (ARBG), as well as it was also not

observed differences between users of ARB (ARBG) and individuals from control

group (Table 3).

The relationship between the FEV1/FVC index was higher in users of

ACE inhibitors (ACEIG) when compared to control subjects (Table 3). However, no

differences were observed among users of ACE inhibitors (ACEIG) and ARB users

(ARBG), as well as it was also not observed differences between users of ARB

(ARBG) and individuals from control group (Table 3).

37

DISCUSSION

In this study, we observed that older adults using ACEI have greater

inspiratory (assessed by MIP) as well as expiratory (assessed by MEP) muscle

strength when compared to seniors who do not use this medication.

ACEI may promote beneficial effects on skeletal muscles12 and it

may also reduce morbidity, mortality and physical decline in patients with congestive

heart failure14;31.

The increase observed in MIP and MEP is similar to that found by

Coirault et al.19 study, which evaluated 18 patients with stable chronic heart failure

and observed a 21% increase in their absolute values of MIP after long-term therapy

(6 months) with Perindopril. Moreover, they also reported an increase of 10% of

MEP in these patients. However, this study evaluated only patients taking ACEI and

they did not consider any effect of Angiotensin-II Receptor Blockers.

Similar to data described by Coirault et al.19, we also observed in this

study a greater effect of ACEI or ARB on the MIP than the MEP. This finding could

be explained by the sensitivity of the respiratory muscles to ACEI. The expiration is

also dependent on the abdominal muscles while the inspiration is a function

essentially dependent of diaphragm32, which is primarily composed of type-I muscle

fibers33, providing slow twitch, high oxidative capacity and low glycolytic capacity,

high performance and aerobic endurance34. There are reports that treatment with

ACEI may produce more specific effects on type-I muscle fibers35. In addition, rats

treated with ACEI had a positive effect on muscle capillary and the percentage of

type-I muscle fibers36.

The potential effects of ACEI on the structure and function of skeletal

muscle suggest a number of mechanisms by which the muscle performance can be

38

enhanced by ACE inhibition, including changes on fibers’ types, decrease in

inflammation, increased vascularization to the muscles as well as improvement of

neuromuscular transmission and metabolic efficiency15;34. ACEI inhibitors promote a

shift in myosin heavy chain of skeletal muscle, evoking an stage more resistant to

muscle fatigue, which shows a positive correlation with physical performance37.

Moreover, ACEI increase insulin sensitivity and glucose uptake by skeletal

muscles38.

Considering lung function, it was observed that individuals using

ACEI inhibitors have higher rates of FVC, FEV1 and FEV1/FVC compared to

untreated individuals (CG), being these data in agreement with other studies39.

However, Coirault et al.19, have found contrasting results, since they observed no

changes in pulmonary function after 6 months therapy with an ACEI. Furthermore,

the long-term therapy with ACEI has not been able to make significant changes in

pulmonary function in patients with tuberculosis40. Additionally, other researchers

reported no changes in lung function in patients with or without CPOD41 after a single

dose of ACEI.

Moreover, Guazzi42 demonstrated that ACEI restores the alveolar

permeability in patients with congestive heart failure, while the use of a combination

of Hydralazine and Isosorbide-Dinitrate improved only ventricular function, without

restoring the capillar permeability. In this context, the author suggests an

independent action of renin-angiotensin system’s modulation on lung function.

The mechanisms by which the blockage of ACE could be related to

an improvement in physical performance have not been clarified. Evidence suggests

that the inactivity of the renin-angiotensin system shows anti-inflammatory action in

several systems43. Moreover, a lower ACE activity was associated with improved

39

hemodynamic and tissue oxygenation in patients with CPOD44 as well as an

improved lung function in patients with CHF, by increasing the capacity of the

alveolar capillary diffusion and pulmonary function of these patients45. Furthermore,

the decrease in ACE activity is related to potential effects on pulmonary

inflammation, increased irrigation, improvements in airflow and respiratory muscle

strenght, improved efficiency of oxygen diffusion and functional capacity of skeletal

muscles46.

Regarding the elderly treated with ARB, there was an increase in

inspiratory and expiratory muscle strength in relation to the CG, showing a similar

behavior of ACEI. However, no significant differences were observed in lung function

(assessed by the FVC, FEV1 and FEV1/FVC index), when compared to CG.

Unfortunately, there are no reports in the literature regarding the use of ARB and

possible effects on respiratory muscle strength and pulmonary function.

From these results, it can be suggested that the beneficial effect

observed by treatment with ACE inhibitors may be at least partially be mediated by

bradykinin, since the ACEI reduce the bradykinin degradation, which evokes release

of endotelium relaxing factors47. The reduction of bradykinin degradation as a result

of ACE inhibition, can increase the blood flow to the skeletal musculature and cause

vasodilation through an increase in capillary density once it promotes glucose and

amino acids uptake, resulting in a greater metabolic efficiency48. These data may

suggest that this beneficial effect on muscle performance is due to the inhibition of

ACE and not only to the pharmacological effects of Angiotensin-II.

Considering the limitations of this study, it may be pointed out that

the diffusion capacity for carbon monoxide was not evaluated. Such information

would be relevant to assess the anatomic and functional integrity of the gas

40

exchange49. Moreover, it would also be important to analyze whether the effect of

ACE would be dose-related as well as monitor the effect of treatment with these

agents over time by cohort studies. Another limitation to consider is the small

number of individuals using ARB (ARBG). It may also be suggested that additional

studies should be performed, especially with larger numbers of patients using this

medication. Moreover, the tests used in this study are volunteer, which means that

they are dependent on the understanding and cooperation of the individual being

tested. Submaximal efforts in the test results can lead to fake measurements30. This

factor may have contributed to some individuals’ exclusion, when the tests were not

performed properly.

Subjects with history of smoking were also excluded even if they had

normal lung function in order to avoid a bias in the results. A study in some regions

from Brazil50 reported that the numbers of elder smokers may reach 31.4% of men

and 10.3% of women. Therefore, this data is consistent with the exclusion of 139

individuals resulting from smoking history.

This study has potentially important implications for public health,

especially to older adults. First, this population show a decline in physical

performance, respiratory muscle strength and pulmonary function2, which may lead

to an increase in mortality risk16. Therefore, measurements or pharmacological

approaches that could prevent this decline are clinically relevant14;15;19. Second, the

benefits of these medication on respiratory muscle strength and lung function could

enhance its recommendation for several diseases6-9 especially in elderly.

41

CONCLUSION

From this study, it can be concluded that physically independent

elderly using Angiotensin-Converting Enzyme Inhibitors have better respiratory

muscle strength and lung function than older adults not using these medication.

Therefore, it may be suggested that therapy with Angiotensin-Converting Enzyme

Inhibitors may attenuate the decline of respiratory function age-related.

42

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3. Neder JA, Andreoni S, Lerario MC et al. Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res 1999;32:719-727.

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7. Williams AG, Day SH, Folland JP et al. Circulating angiotensin converting enzyme activity is correlated with muscle strength. Med Sci Sports Exerc 2005;37:944-948.

8. Scharplatz M, Puhan MA, Steurer J et al. Does the Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy?--A systematic review. Curr Control Trials Cardiovasc Med 2005;6:16.

9. Ziada AM. Additional salutary effects of the combination of exercise training and an angiotensin-converting enzyme inhibitor on the left ventricular function of spontaneously hypertensive rats. J Hypertens 2009;27:1309-1316.

10. Tom B, Dendorfer A, Danser AH. Bradykinin, angiotensin-(1-7), and ACE inhibitors: how do they interact? Int J Biochem Cell Biol 2003;35:792-801.

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inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats. Exp Physiol 2007;92:1047-1056.

13. Bunout D, Barrera G, de la Maza MP et al. Effects of enalapril or nifedipine on muscle strength or functional capacity in elderly subjects. A double blind trial. J Renin Angiotensin Aldosterone Syst 2009;10:77-84.

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14. Onder G, Penninx BW, Balkrishnan R et al. Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 2002;359:926-930.

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16. Buchman AS, Boyle PA, Wilson RS et al. Respiratory muscle strength predicts decline in mobility in older persons. Neuroepidemiology 2008;31:174-180.

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18. Bunout D, Barrera G, Avendano M et al. Results of a community-based weight-bearing resistance training programme for healthy Chilean elderly subjects. Age Ageing 2005;34:80-83.

19. Coirault C, Hagege A, Chemla D et al. Angiotensin-converting enzyme inhibitor therapy improves respiratory muscle strength in patients with heart failure. Chest 2001;119:1755-1760.

20. Dimitriou G, Papakonstantinou D, Stavrou EF et al. Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants. Respir Res 2010;11:57.

21. Vandenbroucke JP, von EE, Altman DG et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Epidemiology 2007;18:805-835.

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27. ATS/ERS Statement on respiratory muscle testing Am J Respir Crit Care Med 2002;166:518-624.

28. Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationship to age and sex. Am Rev Respir Dis 1969;99:696-702.

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29. Miller MR, Hankinson J, Brusasco V et al. Standardisation of spirometry. Eur Respir J 2005;26:319-338.

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31. Mansur SJ, Hage FG, Oparil S. Have the renin-angiotensin-aldosterone

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32. Wu A, Drummond GB. Respiratory muscle activity and respiratory obstruction after abdominal surgery. Br J Anaesth 2006;96:510-515.

33. Stubbings AK, Moore AJ, Dusmet M et al. Physiological properties of human diaphragm muscle fibres and the effect of chronic obstructive pulmonary disease. J Physiol 2008;586:2637-2650.

34. Wang P, Fedoruk MN, Rupert JL. Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents? Sports Med 2008;38:1065-1079.

35. Schaufelberger M, Andersson G, Eriksson BO et al. Skeletal muscle changes in patients with chronic heart failure before and after treatment with enalapril. Eur Heart J 1996;17:1678-1685.

36. Minami N, Li Y, Guo Q et al. Effects of angiotensin-converting enzyme inhibitor and exercise training on exercise capacity and skeletal muscle. J Hypertens 2007;25:1241-1248.

37. Vescovo G, Dalla LL, Serafini F et al. Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition. Circulation 1998;98:1742-1749.

38. Henriksen EJ, Jacob S, Augustin HJ et al. Glucose transport activity in insulin-resistant rat muscle. Effects of angiotensin-converting enzyme inhibitors and bradykinin antagonism. Diabetes 1996;45 Suppl 1:S125-S128.

39. Butorov IV, Butorov SI, Maksimov VV. [Clinical efficiency of course and long-term therapy with the angiotensin-converting enzyme inhibitor perindopril in patients with chronic obstructive lung disease and cor pulmonale]. Probl Tuberk Bolezn Legk 2006;20-24.

40. Kim MA, Lee CH, Kim DK et al. Long-Term Effects of ACE Inhibitors in Post-Tuberculosis Emphysema. Tuberc Respir Dis 69, 418-425. 2010.

41. Ayache AS, Salman V, Traub YM. [Effect of captopril on pulmonary function].

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42. Guazzi M, Agostoni P. Angiotensin-converting enzyme inhibition restores the diffusing capacity for carbon monoxide in patients with chronic heart failure by improving the molecular diffusion across the alveolar capillary membrane. Clin Sci (Lond) 1999;96:17-22.

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43. Fliser D, Buchholz K, Haller H. Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation 2004;110:1103-1107.

44. Kanazawa H, Hirata K, Yoshikawa J. Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study. Thorax 2003;58:629-631.

45. Guazzi M, Marenzi G, Alimento M et al. Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin. Circulation 1997;95:1930-1936.

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47. Vanhoutte PM. Endothelium-dependent responses and inhibition of angiotensin-converting enzyme. Clin Exp Pharmacol Physiol 1996;23:S23-S29.

48. Hespel P, Vergauwen L, Vandenberghe K et al. Significance of insulin for glucose metabolism in skeletal muscle during contractions. Diabetes 1996;45 Suppl 1:S99-104.

49. Neder JA, Andreoni S, Peres C et al. Reference values for lung function tests. III. Carbon monoxide diffusing capacity (transfer factor). Braz J Med Biol Res 1999;32:729-737.

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46

Figure 1- Flowchart of the population enrolled at the study after inclusion/exclusion

criteria.

Asthma or CPOD (8)

47

Table 1 - Distribution of anthropometric data among groups.

Groups

Anthropometric

Data

CG

(n= 150)

ACEIG

(n = 80)

ARBG

(n = 22)

p

Gender M 52 (34.67%) 21 (26.25%) 06 0.39

F 98 (65.33%) 59 (73.75%) 16

Age (years)* 69.0 ± 6.6 67.8 ± 6.3 68.2 ± 4.3 0.36

Height (cm)* 156.4 ± 9 157.4 ± 10 154.8 ± 8 0.48

Weight (Kg)* 67.4 ± 11.3 70,4 ± 13,2 71,9 ± 17,6 0.11

BMI* 27.3 ± 3.8 28.6 ± 4.3 28.6 ± 5.1 0.05

Male (M), Female (F), Body mass index (BMI), Control group (CG), Angiotensin Converting Enzime Inhibitor Group (ACEIG), Angiotensin-II Receptor Blockers Group (ARBG). * Values are expressed as mean and standard deviation (Mean ± SD).

48

TABLE 2 - Comparison of the respiratory muscle strength among groups.

Groups

Respiratory

muscle strenght

CG

(n=150)

ACEIG

(n=80)

ARBG

(n=22)

p

MIP (%pred) 93.2

(80.2 – 110.3)

102.2 *

(86.1 – 135.9)

109.7 *

(89.95 – 130.4)

0.001

MEP (%pred) 103.1

(80.1 – 132.4)

119.9 *

(93.93 – 140.9)

103.7 *

(86.65 - 148)

0.003

Control group (CG), Angiotensin Converting Enzime Inhibitor Group (ACEIG), Angiotensin-II Receptor Blockers Group (ARBG). Values are expressed in Median and Interquartile Interval (1st.Q. - 3rd.Q.). * Statistically different than control group (Kruskal-Wallis test followed by Dunn´s test).

49

Table 3 - Comparison of data pulmonary function among groups.

Groups

Pulmonary

Function

CG

(n= 150)

ACEIG

(n = 80)

ARBG

(n = 22) p

FVC(%pred)

86.65

(81.37 – 95.84)

92.47 *

(84.08 – 98.75)

87.87

(82.74 – 96.07)

0.010

FEV1(%pred)

90.5

(83.25 - 99)

97 *

(88.25 – 104.8)

89

(83 – 103.5)

0.001

FEV1/FVC(%)

102

(97-107)

106 *

(101 - 110.8)

106.5

(103.5 - 109) 0.003

Control group (CG), Angiotensin Converting Enzime Inhibitor Group (ACEIG), Angiotensin-II Receptor Blockers Group (ARBG). Values are expressed in Median and Interquartile Interval (1st.Q. - 3rd.Q.).

* Statistically different than control group (Kruskal-Wallis test followed by Dunn´s test).

50

4. CONCLUSÃO GERAL

A partir deste estudo, pode-se concluir que idosos fisicamente

independentes usuários de IECA apresentam melhor força muscular respiratória e

melhor função pulmonar que idosos não usuários destes medicamentos.

Desta forma, sugere-se que a terapia com IECA poderia atenuar o

declínio da função respiratória relacionado ao processo do envelhecimento.

51

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38. Rouyer O, Zoll J, Daussin F et al. Effect of angiotensin-converting enzyme inhibition on skeletal muscle oxidative function and exercise capacity in streptozotocin-induced diabetic rats. Exp Physiol 2007;92:1047-1056.

39. Bunout D, Barrera G, de la Maza MP et al. Effects of enalapril or nifedipine on muscle strength or functional capacity in elderly subjects. A double blind trial. J Renin Angiotensin Aldosterone Syst 2009;10:77-84.

40. Onder G, Penninx BW, Balkrishnan R et al. Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 2002;359:926-930.

41. Onder G, Vedova CD, Pahor M. Effects of ACE inhibitors on skeletal muscle. Curr Pharm Des 2006;12:2057-2064.

42. Dimitriou G, Papakonstantinou D, Stavrou EF et al. Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants. Respir Res 2010;11:57.

43. Coirault C, Hagege A, Chemla D et al. Angiotensin-converting enzyme inhibitor therapy improves respiratory muscle strength in patients with heart failure. Chest 2001;119:1755-1760.

44. Buchman AS, Boyle PA, Wilson RS et al. Respiratory muscle strength predicts decline in mobility in older persons. Neuroepidemiology 2008;31:174-180.

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45. Pascual Figal DA, Morena Valenzuela GL, Nicolas RF et al. [Addition of an angiotensin II receptor blocker to maximal dose of ACE inhibitors in heart failure]. Rev Esp Cardiol 2002;55:862-866.

46. Khalili MA, Elkins MR. Aerobic exercise improves lung function in children with intellectual disability: a randomised trial. Aust J Physiother 2009;55:171-175.

47. Garcia-Aymerich J, Lange P, Benet M et al. Regular physical activity modifies smoking-related lung function decline and reduces risk of chronic obstructive pulmonary disease: a population-based cohort study. Am J Respir Crit Care Med 2007;175:458-463.

48. Farid R, Azad FJ, Atri AE et al. Effect of aerobic exercise training on pulmonary function and tolerance of activity in asthmatic patients. Iran J Allergy Asthma Immunol 2005;4:133-138.

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81. Smith CG, Vane JR. The discovery of captopril. FASEB J 2003;17:788-789.

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83. Mansur SJ, Hage FG, Oparil S. Have the renin-angiotensin-aldosterone system perturbations in cardiovascular disease been exhausted? Curr Cardiol Rep 2010;12:450-463.

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89. Woods DR, Pollard AJ, Collier DJ et al. Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene and arterial oxygen saturation at high altitude. Am J Respir Crit Care Med 2002;166:362-366.

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90. Dimitriou G, Papakonstantinou D, Stavrou EF et al. Angiotensin-converting enzyme gene polymorphism and respiratory muscle function in infants. Pediatr Pulmonol 2010;45:1233-1239.

91. Jones A, Woods DR. Skeletal muscle RAS and exercise performance. Int J Biochem Cell Biol 2003;35:855-866.

92. Wang P, Fedoruk MN, Rupert JL. Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents? Sports Med 2008;38:1065-1079.

93. Ramalho FS. A regeneração hepática e os inibidores da enzima conversora da angiotensina. Acta Cir. Bras. 2000; 15 Suppl 2:14-17.

94. Sharma JN. Hypertension and the bradykinin system. Curr Hypertens. Rep. 2009;11:178-81.

95. Burnier M, Waeber B, Brunner HR. The advantage of the angiotensin II antagonism. Journal of hypertension 1994;12:S7-15.

96. Flint L. The role of ACE inhibitor therapy in treating cardiovascular disease. Nurs Times 2004;100:34-37.

97. Goodman LS, Hardman JG, Limbrid LE. Goodman & Gilman: As bases farmacológicas da terapêutica. 2006. Mc Graw Hill.

98. Serafin-Bromblik J, Bartula M, Marcisz C. [Angiotensin converting enzyme inhibitors and respiratory system]. Pol Merkur Lekarski 2006;21:286-290.

99. Angeli F, Verdecchia P, Reboldi GP et al. Meta-Analysis of effectiveness or lack thereof of angiotensin-converting enzyme inhibitors for prevention of heart failure in patients with systemic hypertension. Am J Cardiol 2004;93:240-243.

100. Vasan RS, Evans JC, Larson MG et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 2004;351:33-41.

101. Lynn H, Kwok T, Wong SY et al. Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. Bone 2006;38:584-588.

102. Dias da Silva VJ, Montano N, Salgado HC et al. Effects of long-term angiotensin converting enzyme inhibition on cardiovascular variability in aging rats. Auton Neurosci 2006;124:49-55.

103. Williams BR, Kim J. Cardiovascular drug therapy in the elderly: theoretical and practical considerations. Drugs Aging 2003;20:445-463.

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106. Oda T, Hirata M, Oshida Y et al. Effect of imidapril, an angiotensin-converting enzyme inhibitor, on fructose-induced insulin resistance in rats. Endocr J 2004;51:69-74.

107. Nakagawa H, Daihara M, Tamakawa H et al. Effects of quinapril and losartan on insulin sensitivity in genetic hypertensive rats with different metabolic abnormalities. J Cardiovasc Pharmacol 1999;34:28-33.

108. Henriksen EJ, Jacob S, Augustin HJ et al. Glucose transport activity in insulin-resistant rat muscle. Effects of angiotensin-converting enzyme inhibitors and bradykinin antagonism. Diabetes 1996;45 Suppl 1:S125-S128.

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110. Gambassi G, Lapane KL, Sgadari A et al. Effects of angiotensin-converting enzyme inhibitors and digoxin on health outcomes of very old patients with heart failure. SAGE Study Group. Systematic Assessment of Geriatric drug use via Epidemiology. Arch Intern Med 2000;160:53-60.

111. Naeije R. Breathing more with weaker respiratory muscles in pulmonary arterial hypertension. Eur Respir J 2005;25:6-8.

112. Miller MR. Structural and physiological age-associated changes in aging lungs. Semin Respir Crit Care Med 2010;31:521-527.

113. Beaty TH, Newill CA, Cohen BH et al. Effects of pulmonary function on mortality. J Chronic Dis 1985;38:703-710.

114. Harada J, Sekizawa K. Angiotensin-converting enzyme inhibitors and pneumonia in elderly patients with intracerebral hemorrhage. J Am Geriatr Soc 2006;54:175-176.

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117. Abraham MR, Olson LJ, Joyner MJ et al. Angiotensin-converting enzyme genotype modulates pulmonary function and exercise capacity in treated patients with congestive stable heart failure. Circulation 2002;106:1794-1799.

118. Guazzi M, Palermo P, Pontone G et al. Synergistic efficacy of enalapril and

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losartan on exercise performance and oxygen consumption at peak exercise in congestive heart failure. Am J Cardiol 1999;84:1038-1043.

119. Guazzi M, Agostoni P. Angiotensin-converting enzyme inhibition restores the diffusing capacity for carbon monoxide in patients with chronic heart failure by improving the molecular diffusion across the alveolar capillary membrane. Clin Sci (Lond) 1999;96:17-22.

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122. Riska H, Stenius-Aarniala B, Sovijarvi AR. Comparison of the effects of an angiotensin converting enzyme inhibitor and a calcium channel blocker on blood pressure and respiratory function in patients with hypertension and asthma. J Cardiovasc Pharmacol 1987;10 Suppl 10:S79-S81.

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APÊNDICE

61

APÊNDICE A

Questionário de Comorbidades e Consumo de Medicamentos.

Nome: ......................................................................................................................................................

Data: ........................................

1) O Sr./Sra. teve alguma doença grave no passado? Sim Não

Se sim,

qual?……………………………………………………………………................................................

Com qual idade (teve diagnóstico?)

………………….............................................................................................................................

2) O Sr./Sra. tem:

Doença pulmonar / respiratória Sim Não

asma enfisema bronquite outra

qual?______________

Doença reumática Sim

Não

artrite artrose gota outra

qual?______________

Doença do coração Sim

Não

arritmia infarto cir.revasc. ins.card.

outra qual?______________

Pressão alta Sim

Não

Diabetes Sim

Não

Osteoporose Sim

Não

Problema de tireóide (qual?) Sim

Não

hipotireodismo hipertireoidismo outro

qual?______________

Problema vascular (qual?) Sim

Não

trombose IAPC varizes AVE outro

qual?______________

Alergia (a quê?) Sim

Não

poeira prod. químico animais outra

qual?______________

Doença cardíaca na família

(qual?) Sim

Não

arritmia infarto cir. revasc. outra

qual?______________

Doença gastrointestinal Sim

Não

gastrite úlcera constipação outra

qual?______________

Doença neurológica Sim

Não

Alzheimer Parkinson outro

qual?______________

62

3) O Sr./Sra. toma alguma medicação no momento? Se sim, preencha a tabela abaixo.

Sim Não

Medicamento Posologia Via de adm Duração do tto Efeito colateral

4) Relacionar cada medicamento, com as seguintes informações:

Indicação

( ) Médico ou Dentista

( ) Farmacêutico

( ) Equipe de Saúde da UBS

( ) Amigos ou Automedicação

5) Local de Aquisição do medicamento

( ) Posto de Saúde

( ) Hospital

( ) Farmácia

( ) UBS

( ) Outro/Não sabe

6) Recebeu orientação

( ) Sim

( ) Não

( ) Não lembra

7) Se afirmativo, de quem?

( ) Médico ou Dentista

( ) Farmacêutico

( ) Equipe de Saúde da UBS

( ) Amigos, parentes

( ) Automedicação

( ) Outros

63

ANEXOS

64

ANEXO A

65

ANEXO B – Normas de formatação do periódico Journal of the American

Geriatrics Society

Journal of the American Geriatrics Society

© The American Geriatrics Society

Edited By: Thomas T. Yoshikawa

Impact Factor: 3.913

ISI Journal Citation Reports © Ranking: 2010: 2/28 (Gerontology); 2/30

(Gerontology); 9/44 (Geriatrics & Gerontology)

Online ISSN: 1532-5415

Author Guidelines

The primary goal of the Journal of the American Geriatrics Society (JAGS) is to

publish articles that are relevant in the broadest terms to the clinical care of older

persons. The Journal only considers studies involving human participants. Such

articles may span a variety of disciplines and fields and may be of immediate,

intermediate, or long-term potential benefit to clinical practice. In the review process,

equal weight will be placed on innovation and quality of the study design or review

methodology.

All inquiries about the Journal should be addressed to the Journal of the American

Geriatrics Society, VA Greater Los Angeles Healthcare Systems, 11301 Wilshire

Blvd., Bldg. 220, Room 309, Los Angeles, CA 90073; telephone (310) 482-3717; fax

(310) 425-3296, email: [email protected]

mailto:[email protected]

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AUTHORSHIP AND DUPLICATE PUBLICATIONS

The Journal adheres to the Uniform Requirements for manuscripts Submitted to

Biomedical Journals established by the International Committee of Medical Journal

Editors (ICMJE;www.icmje.org), and authors should adhere to these requirements.

The principles of this document, including those related to overlapping (duplicate)

publication, authorship, and disclosure of potential conflict of interest, apply equally

to manuscripts for consideration in thisJournal or in a separate supplement.

All authors should meet the ICJME criteria for authorship. In particular, for byline

authors, authorship credit should be based on 1) substantial contributions to

conception and design, or acquisition of data, or analysis and interpretation of data;

2) drafting the article or revising it critically for important intellectual content; and 3)

final approval of the version to be published. Authors should meet conditions 1, 2,

and 3. All persons designated as authors must qualify for authorship, and all those

who qualify should be listed. The letter accompanying the manuscript should include

the statement, “All authors meet the criteria for authorship stated in the Uniform

Requirements for Manuscripts Submitted to Biomedical Journals.” Within the

Acknowledgment section and under the subheading “Author's Contributions,” all

authors’ specific areas of contributions should be listed. In addition, any writer or

editor assisting the authors but who does not fulfill all criteria for authorship should

be acknowledged in the manuscript, including a description of their role in the paper,

affiliation(s), and source(s) of support. (For example, a professional or medical writer

who prepares a manuscript on behalf of another author (“ghost writer”) should not be

listed as an author but his/her specific role should be stated in this section.)

Manuscripts purporting to contain original material will be considered for publication

with the understanding that neither the article nor any of its essentials, including

tables and figures, has been or will be published or submitted for publication

elsewhere before appearing in this Journal. When submitting a paper, the author(s)

should always make a full statement to the editor in chief about all submissions and

previous reports that might be regarded as redundant, duplicate or overlapping

significantly with the presently submitted paper to JAGS. The author(s) should also

alert the editor in chief if the current (JAGS) research includes subjects about which

a previous report has been published. Such research should be referred to and

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referenced in the JAGSpaper. In the event that the research uses a database from

which one or more other papers have been previously published, the manuscript

submitted to JAGS need not reference all papers previously published from the

database but should reference those previous papers that are pertinent to the

submission. The editor in chief will assess the information provided by the author(s)

and subsequently may request copies of such previously published, in-press, or

submitted (to another journal) papers before further review is permitted. Details on

what constitutes duplicate papers, why duplicate publications arise, and what steps

might be taken with duplicate publications can be found in an editorial statement by

Tobin MJ, “AJRCCM’s Policy on Duplicate Publication,” American Journal of

Respiratory and Critical Care Medicine (2002; 166:433-434), which can be accessed

on the Internet by logging on

tohttp://ajrccm.atsjournals.org/cg/content/full/166/4/433. In addition, a statement by

the International Committee of Medical Journal Editors on “Redundant or Duplicate

Publication” can be found in their paper, “Uniform Requirements for Manuscripts

Submitted to Biomedical Journals,” by logging on to www.icmje.org. This rule does

not apply to abstracts or press reports published as a result of a scientific

meeting. ALL MANUSCRIPTS MUST BE SUBMITTED ON-LINE. Plagiarism is

forbidden.

Authors should be aware that the Journal uses anti-plagiarism software (iThenticate)

to screen all manuscripts for plagiarism. Please carefully review and adhere to the

instructions for submitting your papers posted on our

Website:http://mc.manuscriptcentral.com/jags

All manuscripts will be initially reviewed by the editor in chief. If further review is

deemed appropriate, the paper will be assigned to an associate or section editor. If

the paper is judged to be suitable for possible publication, it will be sent to two or

more external referees (reviewers) or, in rare instances, accepted outright with or

without minor revisions. The Journal does not accept two-part articles involving

clinical studies. Rarely, two-part papers may be accepted for review articles (e.g.,

Clinical Management of the Geriatric Patient, Geriatric Bioscience), if the editor in

chief determines that the content or subject matter warrants such a lengthy review.

http://ajrccm.atsjournals.org/cg/content/full/166/4/433

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Authors may indicate the names of potential referees as well as those whom they

wish not to review the paper, but the editor(s) will make the final choice. Manuscripts

held for major revision will be retained for a maximum of 60 days; minor revision

has 30 days. Authors who plan to resubmit but cannot meet this deadline should

contact the editorial office; otherwise, the online system will prevent you from

uploading the manuscript in the system and the paper may be withdrawn or rejected

by the editor in chief. Other types of revisions have similar deadlines but the online

system will not prevent you from uploading your paper if submission is delayed. If the

authors fail to provide a response to a requested revision of their manuscript within

180 days, their paper will be automatically withdrawn.

The guidelines for publication conform to those of the International Committee of

Medical Journal Editors “Uniform Requirements for Manuscripts Submitted to

Biomedical Journals.” The complete document appears in the Annals of Internal

Medicine (1997;126:36–47) and the New England Journal of

Medicine (1997;336:309–315). An explication of statistical guidelines is presented in

John C. Bailar III and Frederick Mostellor, “Guidelines for Statistical Reporting in

Articles for Medical Journals,” Annals of Internal Medicine (1998;108:266–273), as

well as American Medical Association, “AMA Manual of Style. A Guide for Authors

and Editors”. 10th edition. New York: Oxford University Press, 2007.

The research reported in submitted manuscripts must comply with the ethical rules

for human experimentation that are stated in the Declaration of Helsinki

(JAMA 1997;277:925–926), including approval of an institutional review board – or

human experimentation committee – and informed consent. Authors must disclose

this compliance in the Methods section of the manuscript.

WEBSITE SUBMISSION

Manuscripts must be submitted for review via the JAGS Website

at:http://mc.manuscriptcentral.com/jags. Step-by-step instructions for formatting and

uploading manuscripts are available on the opening screen of the site. In preparing

for submission, place the text, tables, and figures in one file. Save your document,

including text and graphic, as a Word document. Type all manuscripts using a 12-

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69

point font size, set text margins at 1” from edge, insert page numbers and do a

continuous line number on your manuscript from abstract to acknowledgment

page only (exclude line numbers for references and graphics). Also, double-

space all elements of the paper including abstract, text, references, tables,

figures, and legends.

TITLE PAGE

The title page should include all authors’ names (first name, middle initial(s), last

name), with highest academic degree(s) (no professional organizations, membership

into society, or certification, e.g., FACP, FRCP, etc., except for AGSF) and all

relevant institutional and corporate affiliations and titles of each author. Specify all

funding sources (grants or institutional or corporate support) and the meeting, if any,

at which the paper was submitted. Also specify the name, address, telephone

number, fax number, and e-mail address of the corresponding author and an

alternate corresponding author (if there is more than one author).

ABBREVIATED TITLE

On the title page, type, in 45 characters or less, the essence of the title should be

used as a running head.

ABSTRACT

JAGS requires that abstracts of manuscripts submitted for the Clinical Investigations,

Brief Reports, and Brief Methodological Reports sections be in a structured form

conforming to guidelines published in the Journal of the American Medical

Association (1998;280:23–24) andAnnals of Internal Medicine (1990;113:69–76).

Abstracts should include the following headings: Background/Objectives, Design,

Setting, Participants, Intervention (if any), Measurements, Results, and Conclusion.

Specify the sample size. Emphasize clinical relevance in the abstract’s conclusion.

Abstract should be limited to 275 words or less for these 3 sections. Full papers

submitted to other sections (e.g., Nursing, Geriatric Bioscience, Education and

Training, etc.) require a simple narrative abstract of 250 words or less summarizing

the content of the paper. Controversies in Geriatrics and Gerontology, Editorials, Old

70

Lives Tales, Clinical Trials and Tribulations, and Letters to the Editor do not require

an abstract.

KEY WORDS

Authors should include 3 to 5 key words at the end of the abstract for all papers

except Editorials, Old Lives Tales, Clinical Trials and Tribulations, and Letters to the

Editor.

TEXT

All clinical studies should include the following headings: INTRODUCTION,

METHODS, RESULTS, DISCUSSION, ACKNOWLEDGMENTS, REFERENCES,

and GRAPHICS (tables, figures or appendices) in that order. Start each of these

sections on a new page. Statistical methodology should be part of the METHODS

section. Do not use “NS” for nonsignificant values. Provide nonsignificant and

significant P-values to no more than three places past the decimal. Use P <.001 for

all P values less than .001. For percentages use no more than one place past the

decimal. In referring to cases with 50 or fewer subjects, state number (“one of four”

cases), rather than percentages (25%). For instruments or scales, indicate normal

range in the table (footnote) or figure as well as in the text if reference is made to

these in this section.

REFERENCES

Number all references in the sequence in which they first appear in the text and use

the style indicated in the “Uniform Requirements for Manuscripts Submitted to

Biomedical Journals.” Abbreviate the title of the journal as done in the Index Medicus

or PubMed. Do not italicize or add periods to the names of the journals. Include only

references that are accessible to all readers. For source material obtained online,

indicate author, title, website address and date accessed. Abstracts are not

acceptable as references unless they have been published in established sources

within the preceding 4 years. Cite only the names of the first three authors

followed by “et al.” and do not place periods after initials of first and middle

names or commas between surnames and first names. Include both the first and

last pages of all references. Manuscripts accepted for publication may be referenced

with page numbers indicated as 000–000. Do not cite by number or list as a

71

reference personal communications or manuscripts in preparation or submitted for

publication. Such material and attribution may be included in the text, if necessary.

References to software programs should also be included in the text (“Analyses were

performed using SAS, version 6.0 (SAS Institute, Inc., Cary, NC)”).

Examples of appropriate reference style:

Journal

1. Mulrow CD, Aguilar C, Endicott JE et al. Quality-of-life changes and hearing

impairment: A randomized trial. Ann Intern Med 1990;113:188–194. (NOTE: List only

first 3 authors’ names and then “et al.”).

Book Chapter

1. Davidson JM. Sexuality and aging. In: Hazzard WR, Andrew R, Bierman EL et

al., eds. Principles of Geriatric Medicine and Gerontology, 2nd Ed. New York:

McGraw-Hill, 1990, pp 108–118.

Book

1. Kane RL, Ouslander JG, Abrass IB. Essentials of Clinical Geriatrics, 2nd Ed.

New York: McGraw-Hill, 1990.

Online

1. ACR Fact Sheet. Osteoarthritis 2000. American College of Rheumatology

(online). Available at:www.rheumatology.org/patients/factsheets/oa/html. Accessed

August 23, 2002.

TABLES

Tables (as well as Figures and Appendices) should appear after the References

section and not in the body of the text or as a separate document. Number all tables

with Arabic numbers consecutively in order of appearance. Type each table double-

spaced on a separate page. Title should have the first letter of each word as upper

case (except prepositions, conjunctions and articles). Every table must have a

caption typed above the tabular material. Symbols for units should be used only in

column headings. Every column must have a description or heading. Do not use

internal horizontal or vertical lines; place horizontal lines between table caption and

column headings, under column headings, and at the bottom of the table (above the

footnotes, if any). Do not submit tables as photographs. Indicate normal range for

http://www.rheumatology.org/patients/factsheets/oa/html

72

instruments or scales. All abbreviations used in tables must be spelled out as

footnotes.

FIGURES

Figures should appear after the References section and either before or after tables,

but not as a separate document. Legends for figures should be presented in

numerical order on a separate page(s), not on or below the figure. All abbreviations

must be spelled out on the figure legend. Indicate normal range for instruments or

scales. Original artwork or figures may be requested upon acceptance of the

manuscript for publication and will not be returned. Figures should be in black and

white. The cost of publishing illustrations in color must be borne by the author

(presently $1,500 per figure for the hard copy and $100 for the online version of the

paper).

There are three preferred formats for digital artwork submission: Encapsulated

PostScript (EPS), Portable Document Format (PDF), and Tagged Image File Format

(TIFF). We suggest that line art be saved as EPS files. Alternatively, these may be

saved as PDF files at 600 dots per inch (dpi) or better at final size. Tone art, or

photographic images, should be saved as TIFF files with a resolution of 300 dpi at

final size. For combination figures, or artwork that contains both photographs and

labeling, we recommend saving figures as EPS files, or as PDF files with a resolution

of 600 dpi or better at final size. More detailed information on the submission of

electronic artwork can be found at http://authorservices.wiley.com.

FOOTNOTES

Footnotes should be used for author affiliations and for explanatory or clarification

remarks in tables and figures. Please use lower case English alphabet starting with

a, b, c, etc., in superscript format RATHER THAN superscript symbols (as previously

instructed by JAGS). Parenthetical statements are more appropriate than footnotes

in the text and should be placed in the text within parentheses.

ACKNOWLEDGMENTS

The corresponding author must affirm that he or she has listed everyone who

contributed significantly (see section on “Authorship and Duplicate Publication”) to

the work and has obtained written consent from all contributors who are not authors

http://authorservices.wiley.com/

73

and are named in the Acknowledgment section. The Acknowledgment section

should clearly list three sections: Conflict of Interest, Author Contributions, and

Sponsor's Role as described below. It is ultimately the corresponding author’s

responsibility to notify all coauthors that the manuscript has been submitted to JAGS,

of all changes in the revised versions, and the final decision of the Editor in chief

of JAGS on the paper, as well as assuring the correct spelling of all authors, order of

authorship, and author affiliations.

Conflict of Interest: The issue of conflict of interest (COI) is of great importance

to JAGS in order to maintain integrity, accuracy and objectivity in material submitted

for publication.

1. There must be adequate and full disclosure of potential conflicts. To facilitate

this process, the following definitions should be helpful:

a. Financial conflicts: employment or affiliation, grants or funding, honoraria,

speaker forum membership, consultant, stock ownership or options (excluding

mutual funds), royalties, expert testimony, advisory board, or patents (pending, filed,

or received) as they relate to the sponsoring agent, products, technology and/or

methodologies involved in the papers submitted for publication. Medical education

companies that are not owned or operated by the sponsoring agent or company

associated with the product, technology or methodology described in the submitted

paper(s) and serve to organize and prepare manuscripts for submission are

generally not considered a potential conflict.

b. Personal conflicts: a close family or personal relationship with owners or

employees of the sponsoring agent or company associated with product, technology

or methodology described in the submitted paper.

c. Full or adequate disclosure:each author addresses each of the specific

categories of financial and personal conflicts.

d. Potential conflict: any circumstance or competing interest that could be

construed or perceived as influencing the interpretation of the results. The time

period for applying the criteria for COI is 3 years prior to the time the manuscript is

submitted (submission date) to the Journal.

2. The Journal will require that each author provide information on each of the

elements of financial and personal conflicts by submission of a COI checklist

accompanying the manuscript (See Table below for suggested format). If there is

74

some doubt about a potential conflict, indicate “yes” for that element and provide a

brief explanation. The editor/editorial office will review the COI document and provide

a summary of any COI within the Acknowledgment section of the manuscript under

the subheading “Conflict of Interest” (which will replace the previous subheading

“Financial Disclosure”). For example, if no conflicts were apparent, we will

indicate: “The editor finds no conflicts of interest for any of the authors.” Alternatively,

if a conflict is noted: “The editor noted that Joe Smith (fictitious name) declares grant

support and honoraria from X company.” The COI document will be kept in the

editorial office file for only accepted manuscripts and for a period of 1 year after

publication date. However, a COI document must be submitted with each new

manuscript (not revisions), regardless if a prior COI statement was provided with a

previously submitted or accepted paper. Failure to submit a complete COI document

with each paper will result in termination of further review of the paper. Please note

that the authors must continue to complete the statement under the subheading

“Author’s Contributions” (as noted previously) and “Sponsor’s Role” within the

Acknowledgment section.

3. The editor in chief and deputy editor will make the determination if there is

adequate or full disclosure of COIs based on review of the paper, COI checklist, and

information provided by other editors and referees. The editor in chief/executive

editor will contact the author(s) if there appears to be lack of adequate or full

disclosure of COIs. The author(s) can submit a rebuttal. Following a rebuttal (or if no

rebuttal is provided), the decision by the editor in chief/deputy editor will be final.

4. The Journal will publish any identified COIs that were not previously reported,

in a future issue of JAGS as an erratum.

5. Any or all authors identified as failing to adequately or fully disclose COIs

will be banned from submitting future manuscripts to JAGS for a minimum

period of 2 years, which will be imposed from the date such a decision is made

by the editor in chief/deputy editor.

6. The COI policy also applies to all editors and

reviewers/referees. However, they are not required to submit a COI document but

must decline reviewing a paper if a COI potentially exists as defined above. Failure

to fully disclose a COI involving a paper under review may lead to disciplinary

actions by the editor in chief including ban from future reviewing of manuscripts,

dismissal from the editorial board, and/or resignation as an editor. If a reviewer or

75

editor is uncertain if a COI exists, (s)he should contact the editor in chief for

consultation.

Author Contributions: Indicate authors’ role in study concept and design,

acquisition of subjects and/or data, analysis and interpretation of data, and

preparation of manuscript. (See section on “Authorship and Duplicate Publication”).

Sponsor’s Role: Indicate sponsor’s role in the design, methods, subject recruitment,

data collections, analysis and preparation of paper.

UNITS OF MEASUREMENT

Although JAGS accepts the use of conventional units of le Système International

d’Unités (SI), we do prefer units of measurements most familiar to those working in

the United States (e.g., mg/deciliter, cells/microliter instead of mg/liter, cells/liter).

ABBREVIATIONS

Abbreviations are acceptable provided they are commonly used or well recognized,

but the use of many abbreviations in a single manuscript is discouraged.

Abbreviations should be given only if the term is used more than one time. Terms

must also be spelled out and followed by the abbreviation in parentheses when first

used in the abstract and text. Terms must also be spelled out in tables and figures,

with abbreviations provided in parentheses immediately following first use of the term

or as footnotes. Abbreviations of units of measurement are not discouraged, but

units of time should not be abbreviated except in virgule construction (e.g., 40

mg/d).

DRUG NAMES

Generic names should be used whenever possible. Brand names may be included in

parentheses after a generic name the first time it is used.

PERMISSIONS

Use or reproduction of materials from other sources (e.g., journal, book) must be

accompanied by a statement or document from both author and publisher giving

permission to JAGS for reproduction.

ACCEPTED MANUSCRIPTS

76

Authors are instructed to e-mail a copy of their final accepted paper in MS Word to

the JAGSeditorial staff: [email protected] and [email protected] The

Exclusive License Form (ELF – copyright form) should be faxed to the Editorial

Office: (310) 425-3296, scanned and emailed to [email protected], or mailed to

Journal of the American Geriatrics Society, VA Greater Los Angeles Healthcare

System, 11301 Wilshire Blvd., Bldg. 220, Room 309, Los Angeles, CA 90073

EARLY VIEW

This feature will allow us to publish articles online in advance of print approximately 8

weeks after the manuscript is received by the Publisher. Articles will be copyedited,

typeset, and posted in their final form, with all author and editor in chief corrections

incorporated. Volume and page numbers will not be added until after the article is

assigned to an issue, but articles will be fully citable using the DOI (digital object

identifier) number provided with the article. To ensure that your article is posted as

quickly as possible, please return your corrected proofs to the proofreader within 48

hours of receipt. Please note that Old Lives Tales, Clinical Trials and Tribulations,

and Letters to the Editor will not be included in the EarlyView section.

EMBARGO POLICY

The Journal proposes two embargo dates – the EarlyView publication and the hard-

copy publication date. The EarlyView embargo date will vary from issue to issue

according to the dates the papers have been posted on the Journal’s website with

their unique citable DOI number. This date will also be considered as the embargo

date for that particular article. Authors can access the EarlyView papers by logging

on to: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1532-5415/earlyview. For

printed issue, press releases will be sent out to reporters on the last day of the

preceding month, with an embargo date of the 9th of the month printed at the top.

Authors must contact the JAGS editorial office before they do a press release.

CATEGORIES OF ARTICLES

To maximize the number of pages that can be published and yet maintain high

quality, there are strict limits on the total number of a) text words, b) graphics (tables,

figures and appendices combined), and c) references. Authors should carefully read

the instructions on abstract format and the limits on the length of the submission

mailto:[email protected]%20%20and%20jags%[email protected]

mailto:[email protected]%20%20and%20jags%[email protected]

http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1532-5415/earlyview

77

based on total text words, number of graphics, and number of references. FAILURE

TO ADHERE TO THESE GUIDELINES AND LIMITS WILL RESULT IN REJECTION

OF THE PAPER.

Sections of JAGS include Clinical Investigations; Brief Reports; Brief Methodological

Reports;Clinical Management of the Geriatric Patient; Geriatric Bioscience; Nursing;

Education and Training; Dental and Oral Health; Aging and Surgery; Drugs and

Pharmacology; Ethics, Public Policy, and Medical Economics; International Health

Affairs; Ethnogeriatrics and Special Populations; Models of Geriatric Care, Quality

Improvement, and Program Dissemination; Updates in Aging; Controversies in

Geriatrics and Gerontology;Special Articles; Editorials; Old Lives Tales; Clinical

Trials and Tribulations; and Letters to the Editor (Case Reports, Research Studies,

and Comments/Responses).

Section Abstract

Text

words

References Graphics

(appendix/table/figure)

Clinical

Investigations

Structured 3,500 50 5

Brief Reports Structured 2,500 30 3

Brief

Methodological

Reports

Structured 2,500 30 3

Clinical

Management of

the Geriatric

Patient

Narrative 5,000 50 5

Geriatric

Bioscience


Ethics, Public

Policy, and

Medical

Economics


Nursing Narrative 3,000 30 3

Education and Narrative 3,000 30 3

78

Training

Dental and

Oral Health


Aging and

Surgery


Drugs and

Pharmacology


Ethnogeriatrics

and Special

Populations


International

Health Affairs


Models of

Geriatric Care,

Quality

Improvement,

and Program

Dissemination


Updates in

Aging


Controversies

in Geriatrics

and

Gerontology

None 1,500 10 2

Special

Articles


Editorials None 1,500 20 2

Old Lives Tales None 750 10 1

Clinical Trials

and

Tribulations

None 750 10 1

Letters to the None 750 10 1

79

Editor

Clinical Investigations

These are reports of investigator-initiated research that presents new information.

Information that is already available in textbooks or as common knowledge will not

be considered for review. The subject matter can be very broad as long as it is

relevant to aging conditions in humans.

To improve the quality of reporting randomized, controlled trials (RCTs), it is

recommended that authors adhere to the CONSORT (Consolidated Standards of

Reporting Trials) statement, which consists of a checklist and flow diagram that

authors can use to report RCTs. Authors should refer to the paper, Altman DG,

Schulz KF, Moher D et al. The revised CONSORT statement for reporting

randomized trials: Explanation and elaboration. Annals of Internal Medicine 2001;

134:663-694.

Brief Reports

These are clinical-investigation or clinical-experience reports whose findings are

somewhat preliminary or a clinical study reporting on narrowly focused or limited

findings.

Brief Methodological Reports

These are reports on the use of a variety of self-reported, administered, or

performance-based measures and scales that assess physical, functional, mood,

cognitive, and social domains; the utility of a new method or approach to investigate

a clinical or health problem in older people; or an innovative model or design to

research issues related to healthcare delivery and service.

Clinical Management of the Geriatric Patient

These papers are clinically oriented reviews with a focus on the diagnosis, treatment

and prevention of clinical problems occurring in older adults. The review should

include a briefdiscussion on epidemiology and current concepts on pathogenesis as

it applies to aging, with amajor focus on how aging impacts clinical manifestations,

diagnostic approach, therapeutic intervention and prevention measures.

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Geriatric Bioscience

Geriatric Bioscience articles are reviews of pathophysiology, pathogenesis or basic

scientific information relevant to a geriatric condition or problem. The paper should

be written in a style, format and language understandable to our readers, who are

predominantly clinicians and not basic scientists. This section should not focus on

animal studies.

Ethics, Public Policy, and Medical Economics

These papers are concerned with ethical issues and economic, political,

environmental, or other issues of public policy that are particularly relevant to the

practice of geriatric medicine. The editors will solicit papers on public policy issues,

but spontaneous submissions are also encouraged.

Nursing

Papers focusing on issues related to nursing research, care, training, education,

policies, etc., will be published in this section. However, research papers on nursing

will generally be published in other sections.

Dental and Oral Health

This section is intended to address dental care, oral health and oral disease as they

impact the geriatric population. With a focus on geriatric dental and oral health

issues, papers can address such areas as original research, program development,

dental care in non-traditional settings, workforce issues and reviews of topics that

would add new knowledge or recommendations for care.

Aging and Surgery

This section is seeking papers of high quality research from leaders within the

surgical community focusing on geriatric care, including outcomes of surgical

procedures with respect to age and in comparison to younger counterparts. Papers

focusing on issues of education/training, healthcare delivery and models, and policy

focusing on geriatric surgery are also welcomed.

Education and Training

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This section includes papers on models of education and training, research in

education, policies related to geriatric training and education, and other issues

relevant to teaching.

Drugs and Pharmacology

Reviews on specific drugs or class of drugs, pharmacology, drug prescribing, and

related topics as they apply to older adults, as well as current information on drugs

from the Food and Drug Administration, and pharmaceutical companies, will be

published in this section. We discourage papers that appear to be a marketing

forum for a specific drug or agent.

Ethnogeriatrics and Special Populations

Papers that focus on issues related to health, disease, disability, healthcare delivery,

education, training, research, policies and ethics that are especially unique or

relevant to minority and ethnic groups or special populations (e.g., older victims or

crime, older prisoners) will generally be published in this section. However, papers

involving these groups and special populations may also be published in other

sections of JAGS depending on the emphasis and general applicability of the

information.

International Health Affairs

Current topics on geriatrics and related issues in countries outside the United States

will be published in this section. Papers for this section should be focused on models

and systems of healthcare delivery for older adults for countries or the country in

question. Also, manuscripts on education/training, economics, politics, policies, and

ethics–all related to aging - are also welcomed. In the case of specific country

profiles, authors may find it helpful to view the outline and the standard table of

country profile in JAGS 2000;48:980-984. Clinical research papers should be

submitted in other appropriate sections of the Journal.

Models of Geriatric Care, Quality Improvement, and Program Dissemination

This section offers the opportunity to disseminate information on effective model

programs or services. Descriptive information on the ‘‘who, what, and how’’ of

innovative programs with evidence relevant to effectiveness and potential for

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replication by others is sought. Pure feasibility studies are not appropriate for this

section. Review criteria include: (1) Innovation: does this model add substantially to

existing models of geriatric care? (2) Model Description: is the model described in

sufficient detail to understand what was done? (3) Effectiveness: is there evidence of

effectiveness of the model for clinical outcomes? Randomized clinical trials are

welcome but not required. (4) Evidence of feasible implementation and/or

dissemination to other settings. Our goal is to offer a venue for the timely sharing of

innovative and effective approaches to important clinical problems in the care of

older patients.

Updates in Aging

This section seeks a concise review on a wide range of topics in aging and long-term

care that may not fit in any of the existing sections in JAGS. Examples might be,

“How does aging affect autism?”; “Does aging alter the effects of traumatic brain

injury?”;“What is future role of aging women in society?”

Controversies in Geriatrics and Gerontology

For this section, a different format will be implemented. We seek to discuss a

topic/issue in geriatrics and gerontology (as well as long-term care) that involve two

experts with opposing views on the subject matter. An example might be, “Should

we aggressively treat systolic hypertension in the very old?” Each invited expert will

submit his/her perspective (1,500 text words/10 references/2 graphics for each

expert); as well as a rebuttal to the opposing viewpoint (500 text words/5

references/1 graphic). The assigned associate editor will write a brief (250 words or

less) narrative abstract to introduce the topic/issue.

Special Articles

This section includes papers on history; recommendations for preventive strategies

in geriatrics; reports of meetings, task force, or committee activities; guidelines and

position statements by the American Geriatrics Society; and other topics relevant to

aging but not conforming to any of theJournal’s existing sections.

Editorials

Editorials are invited comments on a specific paper published in the Journal.

Occasionally, opinions or commentary by qualified and respected individuals on a

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highly relevant topic or controversial issue pertinent to aging will be published in this

section at the discretion of the editor in chief.

Clinical Trials and Tribulations

This section features periodic stories about how professionals with healthcare

training and expertise have found the healthcare system difficult to negotiate. These

stories often come from persons who have enrolled in the national organization,

Professionals with Personal Experience in Chronic Care (PPECC). The underlying

idea is that if health professionals in the field cannot make the healthcare system

function as it should, it is certainly in disrepair. Hopefully, these stories will build a

coalition and action for change. For more information about PPECC, visit their

website (www.ppecc.org).

Old Lives Tales

We invite readers to submit stories, experiences, or incidences which have

instructed, saddened or gladdened us as physicians and, above all, taught us

something about the care of the older adult. When describing a particular patient,

permission should be received in writing from him/her (mailed with the manuscript

and diskette) or the personal details changed enough to conceal the person’s

identity.

Letters to the Editor(three categories: Case Reports, Research Studies, and

Comments/Responses)

Letters to the Editor should be brief. One type of letter is an objective, constructive,

and educational critique of a previously published article

in JAGS (Comments/Responses); these should be submitted within 3 months after

publication of the original paper. The editorial office may submit letters critiquing a

paper published in JAGS to the authors of the paper, who will be given 1 month to

reply to the critique. The letter and the reply will usually be published in tandem.

Other letters may discuss matters of general interest to physicians involved in the

care of older patients, interesting clinical or research findings, or brief commentary

on any aspect of aging as it relates to humans. Case reports and preliminary

research findings may also be appropriate for this section. Generally, we do not

publish letters critiquing papers published in other journals.

http://www.ppecc.org/

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