abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC São Paulo, SP, Brazil PsCD58jSJgpzgk8NNBNtJFF 00001 S0066-782X2007000600001 S0066-782X(07)08800601 10.1590/S0066-782X2007000600001 Artigos Originais Aumento do índice de massa corporal em relação a variáveis clínicas e laboratoriais quanto ao sexo em indivíduos sem evidências de cardiopatia Araújo Fernando Yamada Alice Tatsuko Markus Marcello Ricardo Paulista Antelmi Ivana Latorre Maria do Rosário Dias de Oliveira Mansur Alfredo José São Paulo São Paulo Universidade de São Paulo Faculdade de Medicina Instituto do Coração Brazil 06 2007 88 6 624 629 13 03 2007 16 02 2007 12 02 2006 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

FUNDAMENTO: Na prática clínica, atendemos pacientes com diversos índices de massa corporal (IMC), desde pacientes com sobrepeso até pacientes obesos. Esse achado pode ser a única anormalidade clínica aparente. OBJETIVO: Avaliar as variáveis clínicas e laboratoriais associadas com aumento do IMC em mulheres e homens assintomáticos, sem qualquer indício de cardiopatia, a fim de obter dados para substanciar recomendações médicas, em uma amostra de estudo da nossa prática diária. MÉTODOS: Foram estudados indivíduos entre 14 e 74 anos de idade (média de 40,5 anos); 295 eram homens (43,1%) e 389 eram mulheres (56,9%). As relações entre IMC estratificado por sexo e as variáveis clínicas e laboratoriais foram analisadas por meio do coeficiente de correlação de Spearman e regressão linear múltipla. RESULTADOS: A média do IMC das mulheres (26,15 kg/m²) e dos homens (26,33 kg/m²) não apresentou diferença estatisticamente significante. No modelo de regressão linear múltipla, a relação colesterol total/fração HDL-colesterol (CT/HDL-C) (beta= 1,1320; p < 0,001) e a glicose sérica (beta= 0,0233; p = 0,023) foram independentemente correlacionadas com o IMC em mulheres. Nos homens, as variáveis que apresentaram correlação independente com o IMC foram a relação CT/HDL-C (beta= 0,793; p < 0,001) e a idade (beta = 0,0464; p = 0,030). CONCLUSÃO: Em mulheres e homens sem nenhum indício de cardiopatia, a relação CT/HDL-C aumentou com o IMC em ambos os sexos. Outros índices associados ao IMC foram glicose sérica nas mulheres e idade nos homens. As variáveis clínicas e laboratoriais associadas ao índice de massa corporal podem diferir quanto ao sexo.

 Índice de massa corporal dislipidemias fatores de risco saúde pública 23 07 2007

ARTIGO ORIGINAL

Aumento do índice de massa corporal em relação a variáveis clínicas e laboratoriais quanto ao sexo em indivíduos sem evidências de cardiopatia

Fernando Araújo; Alice Tatsuko Yamada; Marcello Ricardo Paulista Markus; Ivana Antelmi; Maria do Rosário Dias de Oliveira Latorre; Alfredo José Mansur

Instituto do Coração - InCor, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP - Brasil

Correspondência

RESUMO

FUNDAMENTO: Na prática clínica, atendemos pacientes com diversos índices de massa corporal (IMC), desde pacientes com sobrepeso até pacientes obesos. Esse achado pode ser a única anormalidade clínica aparente.

OBJETIVO: Avaliar as variáveis clínicas e laboratoriais associadas com aumento do IMC em mulheres e homens assintomáticos, sem qualquer indício de cardiopatia, a fim de obter dados para substanciar recomendações médicas, em uma amostra de estudo da nossa prática diária.

MÉTODOS: Foram estudados indivíduos entre 14 e 74 anos de idade (média de 40,5 anos); 295 eram homens (43,1%) e 389 eram mulheres (56,9%). As relações entre IMC estratificado por sexo e as variáveis clínicas e laboratoriais foram analisadas por meio do coeficiente de correlação de Spearman e regressão linear múltipla.

RESULTADOS: A média do IMC das mulheres (26,15 kg/m2) e dos homens (26,33 kg/m2) não apresentou diferença estatisticamente significante. No modelo de regressão linear múltipla, a relação colesterol total/fração HDL-colesterol (CT/HDL-C) (b= 1,1320; p < 0,001) e a glicose sérica (b= 0,0233; p = 0,023) foram independentemente correlacionadas com o IMC em mulheres. Nos homens, as variáveis que apresentaram correlação independente com o IMC foram a relação CT/HDL-C (b= 0,793; p < 0,001) e a idade (b = 0,0464; p = 0,030).

CONCLUSÃO: Em mulheres e homens sem nenhum indício de cardiopatia, a relação CT/HDL-C aumentou com o IMC em ambos os sexos. Outros índices associados ao IMC foram glicose sérica nas mulheres e idade nos homens. As variáveis clínicas e laboratoriais associadas ao índice de massa corporal podem diferir quanto ao sexo.

Palavras-chave: Índice de massa corporal, dislipidemias/epidemiologia, fatores de risco, saúde pública.

Introdução

Índice de massa corporal (IMC), definido como peso em quilogramas dividido pelo quadrado da altura em metros (kg/m2), representa uma das medidas de avaliação do grau de sobrepeso e obesidade na prática clínica e em estudos epidemiológicos1. Sobrepeso e obesidade, determinados pelo IMC, são considerados atualmente um importante problema de saúde pública em diversos países2,3, inclusive no Brasil4, e estão associados com maior risco de doenças cardiovasculares5 em homens6-8 e mulheres9-11. Em estudos anteriores, a relação do IMC com doenças cardiovasculares apresentou uma associação forte e sistemática com fatores de risco para doenças cardiovasculares, como pressão alta, intolerância à glicose, diabete e dislipidemia12-14.

Na prática clínica, além de pacientes que apresentam maior risco de desenvolver doenças cardiovasculares, atendemos também pacientes com baixo risco cardiovascular que querem ser submetidos a uma avaliação cardíaca completa (check-up). Em muitos desses pacientes, a principal anormalidade identificada na avaliação clínica pode ser um aumento no índice de massa corporal. Além de recomendar mudanças no estilo de vida voltadas para a redução de peso, seria interessante avaliar as variáveis clínicas e laboratoriais associadas ao aumento do IMC, para obter dados sobre os pacientes que atendemos e assim podermos orientá-los na prevenção de doença cardiovascular.

Aventamos a hipótese de que algumas variáveis clínicas e laboratoriais obtidas na prática cotidiana estejam associadas com o aumento no índice de massa corporal e que essa associação possa diferir entre os sexos.

O objetivo deste estudo foi avaliar as variáveis clínicas e laboratoriaisemrelaçãoaoaumentonoIMCetambémquanto ao sexo, em uma coorte de pacientes ambulatoriais que não apresentaram nenhum indício de cardiopatia, após exames clínicos e laboratoriais minuciosos.

Métodos

Tipo e local do estudo - Uma coorte de indivíduos que não apresentaram indícios de cardiopatia após exames clínicos e laboratoriais minuciosos foi estabelecida no Ambulatório Geral de um hospital universitário terciário que também presta atendimento primário e secundário (exame cardiovascular, segundo parecer e avaliação cardíaca pré-operatória).

Amostra e procedimentos – A avaliação incluiu exame clínico cuidadoso, eletrocardiograma e radiografia do tórax. Os pacientes foram classificados em brancos, negros e mulatos. O tabagismo foi avaliado por meio de pergunta durante o exame clínico e os sujeitos foram classificados em fumantes e não-fumantes. Os indivíduos assintomáticos - com exame clínico, eletrocardiograma e radiografia torácica normais - foram convidados a participar do estudo. Os que concordaram foram submetidos a outros exames laboratoriais, além de teste ergométrico em esteira e ecocardiograma transtorácico bidimensional com Doppler.

Os exames laboratoriais incluíram glicemia, colesterol total, lipoproteína de alta densidade (HDL-colesterol), lipoproteína de baixa densidade (LDL-colesterol) ,relação LDL colesterol/HDL - colesterol, triglicérides, ácidoúrico, hormônio tireoestimulante (TSH), creatinina e análise de urina.

Critérios de inclusão – Incluímos no estudo mulheres e homens assintomáticos com mais de 14 anos de idade que apresentaram exame clínico, eletrocardiograma e radiografia do tórax normais.

Critérios de exclusão – Excluímos indivíduos com história de doença cardiovascular, hipertensão sistêmica, doença de Chagas, diabete melito, TSH < 0,05 ou > 8 mg/dl, doença pulmonar obstrutiva crônica, asma, insuficiência renal, doenças inflamatórias crônicas, doenças osteoarticulares, anemia crônica ou neoplasia, além de ecocardiograma ou teste ergométrico anormal.

População do estudo – Seiscentos e oitenta e quatro indivíduos entre 14 e 74 anos (média de 40,6) foram considerados aptos a participar do estudo; 295 (43,1%) eram homens e 389 (56,9%) eram mulheres. Quinhentos e dezesseis indivíduos (75%) eram brancos, 117 (17,1%) eram mulatos, 32 (4,7%) eram descendentes de asiáticos e 22 (3,2%) eram negros.

Variáveis estudadas – Estudamos o índice de massa corporal (kg/m2) em relação ao sexo, tabagismo (perguntado ao indivíduo durante o exame clínico se ele era fumante ou ex-fumante), glicose sérica (mg/dl), colesterol total (mg/ dl), HDL-colesterol (mg/dl), LDL-colesterol (mg/dl), VLDL-coleterol (mg/dl), razão colesterol total/HDL-colesterol (CT/ HDL-C), razão colesterol total/LDL-colesterol (CT/LDL-C) e triglicérides (mg/dl).

Análise estatística – O teste de aderência (goodness of fit) para distribuição normal foi avaliado pelo teste de Kolmogorov-Smirnov. As médias de idade, índice de massa corporal, freqüência cardíaca, pressão sistólica e diastólica, glicose sérica, triglicérides e colesterol total e parcial foram comparadas por sexo com o teste de Mann-Whitney (pois a distribuição das variáveis não foi normal). Subseqüentemente, a análise foi detalhada para comparar o índice de massa corporal de homens e mulheres também em relação ao tabagismo. A relação entre IMC estratificado por sexo e outras variáveis quantitativas foram analisadas com o coeficiente de correlação de Spearman e análise de regressão linear múltipla.

As variáveis com p < 0,20 na análise univariada foram selecionadas para inclusão no modelo de regressão linear múltipla. Esse modelo foi desenvolvido com o procedimento de inclusão progressiva de variáveis (stepwise forward). A variável independente foi mantida no modelo final quando os valores de p eram < 0,05. O modelo de regressão linear múltipla desenvolvido para toda a amostra também foi aplicado na análise de cada estrato. Constatou-se que os modelos finais de cada estrato pelo IMC e sexo eram semelhantes (os dados não são apresentados). No modelo de regressão múltipla, os resultados submetidos à transformação logaritmica foram expressos como 10b. Os cálculos estatísticos foram realizados com o software SPSS (Statistical Package for Social Science) para Windows (versão 10.0).

Aspectos étnicos – O protocolo foi aprovado pelo Conselho de Ética em Pesquisa com Seres Humanos do Hospital, e todos os pacientes assinaram um Termo de Consentimento Livre e Esclarecido.

Resultados

Seiscentos e oitenta e quatro indivíduos, 389 (56,9%) mulheres e 295 (43,1%) homens, foram elegíveis para o estudo. Havia 285 (73%) mulheres brancas e 228 (77%) homens brancos. Oitenta e cinco (22%) mulheres e 75 (25%) homens eram fumantes. Cento e trinta (33,6%) mulheres e 128 (43,2%) homens estavam acima do peso (IMC 25 a 29 kg/m2) e 76 (19,4%) mulheres e 167 (43,2%) homens eram obesos (IMC > 30 kg/m2).

As características basais dos participantes em relação ao sexo revelaram uma diferença significante nos valores médios de glicose sérica (p < 0,001), triglicérides (p < 0,001) e HDL-colesterol (p <0,001) entre homens e mulheres. Outras características basais dos participantes são apresentadas na Tabela 1.

A comparação do IMC médio entre mulheres (26,15kg/m2) ehomens (26,33kg/m2) não relevou diferença estatisticamente significante. Não houve diferença estatisticamente significante também entre o IMC de mulheres fumantes e não-fumantes nem de homens fumantes e não-fumantes (tab. 2).

Em mulheres e homens, a análise univariada revelou uma correlação significante entre IMC e idade, glicose sérica, triglicérides sérico e colesterol total e parcial (tab. 3).

Na análise de regressão múltipla ajustada por sexo foram identificadas as seguintes variáveis independentes associadas com aumento do IMC nos homens: CT/HDL-C (b= 0,793; p < 0,001) e idade (b= 0,0464; p = 0,030); nas mulheres essas variáveis foram CT/HDL-C (b= 1,1320; p < 0,001) e glicose sérica (b = 0,0233; p = 0,023) (tab. 4).

Discussão

Não observamos diferença estatisticamente significante entre o IMC de mulheres e homens, em concordância com estudos anteriores15-17. Em outro estudo, constatou-se que o IMC era influenciado pelo sexo18. Portanto, segundo nossa experiência, o aumento do IMC deve ser motivo de recomendações médicas tanto no caso de homens como de mulheres.

Neste estudo, os valores do índice de massa corporal ficaram entre a faixa mais baixa do IMC dos asiáticos19 e a mais elevada da população européia20 e americana21. Esses achados podem estar relacionados com diferenças nas características das populações estudadas e outras variáveis clínicas e demográficas. Em nossa amostra de pacientes ambulatoriais, os indivíduos estão atingindo o IMC dos europeus e americanos.

Não houve diferença estatisticamente significante no IMC de fumantes e ex-fumantes ou de homens e mulheres. Constatou-se que o abandono do tabagismo e a redução da atividade física aumentam o risco de ganho de peso tanto em homens como em mulheres22. Em outro estudo, sedentarismo em fumantes e ex-fumantes e obesidade em mulheres foram fortes fatores de risco para comprometimento da saúde, como principal efeito de cada variável ou como um efeito combinado (interações)23. Não houve relação entre IMC e tempo de abandono do tabagismo24. Os ex-fumantes tinham IMC mais alto do que os que nunca tinham fumado25. Esse é um achado interessante na amostra do nosso estudo, que nos ajuda a advertir os pacientes sobre a relação entre tabagismo e peso corporal.

Em nosso estudo, a idade foi independentemente correlacionada com o IMC. Em outros estudos, o envelhecimento foi associado com aumento no IMC em homens26,27. Mesmo quando o sobrepeso não representa um problema sério na velhice, idosos obesos certamente correm risco de incapacidade, morbidade e mortalidade28. Acredita-se que o aumento do IMC relacionado ao envelhecimento esteja associado com doença cardiovascular29. Esses achados indicam que os fatores relacionados ao sexo podem participar do ganho ponderal e que precisam ser mais bem estudados.

O índice de massa corporal foi independentemente correlacionado com a glicose sérica nas mulheres deste estudo. Em estudos anteriores, o IMC correlacionou-se positivamente com os níveis de glicose em homens e mulheres30,31. Tanto homens como mulheres, em um acompanhamento de dez anos, apresentaram maior incidência de diabete com o aumento no grau de sobrepeso32. A perda de peso reduziu o risco de coronariopatia em mulheres obesas com resistência à insulina33,44. Os resultados de um estudo que incluiu homens e mulheres forneceu evidências para o estabelecimento de metas de níveis de glicose sérica e IMC em pacientes com baixas concentrações de HDL-C e altas concentrações de triglicérides35.Em nosso estudo, alguns fatores desconhecidos, além dos conhecidos fatores de risco relacionados com a obesidade, podem ser responsáveis por essa observação.

A relação colesterol total/HDL-colesterol na amostra do nosso estudo correlacionou-se de forma independente com o IMC em homens e mulheres. Não detectamos correlação independente entre colesterol total, LDL-colesterol e HDL-colesterol com índice de massa corporal. Esses achados concordam com estudos anteriores realizados apenas com homens36 e com mulheres37 e com homens e mulheres38,39. Alguns estudos demonstraram que a relação colesterol total/HDL-colesterol é um potente marcador lipoprotéico do desenvolvimento de coronariopatia40,41, independentemente dos valores absolutos de LDL-colesterol, HDL-colesterol42 e relação LDL-colesterol/HDL-colesterol43. Os pacientes com relação colesterol total/HDL-colesterol elevada também foram consideravelmente mais resistentes à insulina44.A resistência à insulina também está relacionada com obesidade45. Portanto, outras características metabólicas podem estar envolvidas na fisiopatologia da associação entre a relação colesterol total/ HDL-colesterol e o aumento no índice de massa corporal.

Nosso estudo teve limitações. Analisamos uma amostra de pacientes assintomáticos com exame clínico normal que talvez não represente a população como um todo. Os índices de correlação das variáveis clínicas e laboratoriais associadas como aumento no índice de massa corporal foram modestos, porém significativos. As implicações clínicas desses resultados, especificamente quando analisamos o significado clínico do aumento no IMC, devem ser consideradas em um contexto mais amplo no estudo das variáveis clínicas e laboratoriais associadas. A terapia de reposição hormonal também pode influenciar o índice de massa corporal46,mas não foi avaliada na época do estudo. Entretanto, essa terapia não era comum na população que atendemos.

Concluindo, nossos dados demonstraram que, em homens e mulheres saudáveis sem indícios de cardiopatia, a relação colesterol total/HDL-colesterol aumentava conforme aumentava o IMC tanto em homens como em mulheres. Outros índices associados ao IMC foram glicose sérica em mulheres e idade em homens. A interpretação das variáveis clínicas e laboratoriais associadas com o índice de massa corporal pode se beneficiar do fato de ser mais específica ao sexo.

Fernando Araújo

Rua Mozelos, 13

02073-100 - São Paulo, SP - Brasil

E-mail:

grafernando@incor.usp.br

Artigo recebido em 12/02/06; revisado recebido em 16/02/07; aceito em 13/03/07.

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Obesity as an independent risk factor for cardiovascular disease: a 26 years follow-up of participants in the Framingham Heart Study Circulation 1983 968 77 67 Hubert HB Feinleib M McNamara PM Castelli WP 30. Hu G, Lindstrom J, Valle TT, Eriksson JG, Jousilahti P, Silventoinen K. Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation. Arch Intern Med. 2004;164:892-6. Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation Arch Intern Med 2004 892 6 164 Hu G Lindstrom J Valle TT Eriksson JG Jousilahti P Silventoinen K 31. McLaughlin T, Allison G, Abbasi F, Lamendola C, Reaven G. Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals. Metabolism. 2004;53:495-9. Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals Metabolism 2004 495 9 53 McLaughlin T Allison G Abbasi F Lamendola C Reaven G 32. Field AE, Coakley EH, Must A, Spadano JL, Laird N, Dietz WH, et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med. 2001;161:1581-6. Impact of overweight on the risk of developing common chronic diseases during a 10-year period Arch Intern Med 2001 1581 6 161 Field AE Coakley EH Must A Spadano JL Laird N Dietz WH 33. Ross R, Fortier L, Hudson R. Separate associations between visceral and subcutaneous adipose tissue distribution, insulin and glucose levels in obese women. Diabetes Care. 1996;19:1404-11. Separate associations between visceral and subcutaneous adipose tissue distribution, insulin and glucose levels in obese women Diabetes Care 1996 1404 11 19 Ross R Fortier L Hudson R 34. McLaughlin T, Abbasi F, Kim H, Lamendola C, Schaaf P, Reaven G. Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women. Metabolism. 2001;50:795-800. Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women Metabolism 2001 795 800 50 McLaughlin T Abbasi F Kim H Lamendola C Schaaf P Reaven G 35. Devroey D, De Swaef N, Coigniez P, Vandevoorde J, Kartounian J, Betz W. Correlations between lipid levels and age, gender, glycemia, obesity, diabetes, and smoking. Endocr Res. 2004;30:83-93. Correlations between lipid levels and age, gender, glycemia, obesity, diabetes, and smoking Endocr Res 2004 83 93 30 Devroey D De Swaef N Coigniez P Vandevoorde J Kartounian J Betz W 36. Denke MA, Sempos CT, Grundy SM. Excess body weight: an underrecognized contributor to high blood cholesterol levels in white American men. Arch Intern Med. 1993;153:1093-103. Excess body weight: an underrecognized contributor to high blood cholesterol levels in white American men Arch Intern Med 1993 1093 103 153 Denke MA Sempos CT Grundy SM 37. Denke MA, Sempos CT, Grundy SM. Excess body weight: an underrecognized contributor to dyslipidemia in white American women. Arch Intern Med. 1994;154:401-10. Excess body weight: an underrecognized contributor to dyslipidemia in white American women Arch Intern Med 1994 401 10 154 Denke MA Sempos CT Grundy SM 38. Mahanonda N, Bhur ipanyo K, Leowat tana W, Kangkagate C,Chotinaiwattarakul C, Pornratanarangsi S, et al. Obesity and risk factors of coronary heart disease in healthy Thais: a cross-sectional study. J Med Assoc Thai. 2000;83 (suppl.2):S35-45. Obesity and risk factors of coronary heart disease in healthy Thais: a cross-sectional study J Med Assoc Thai 2000 S35 45 83 Mahanonda N Bhur ipanyo K Leowat tana W Kangkagate C Chotinaiwattarakul C Pornratanarangsi S 39. Brown CD, Higgins M, Donato KA, Rohde FC, Garrison R, Obarzanek E, et al. Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res. 2000;8:605-19. Body mass index and the prevalence of hypertension and dyslipidemia Obes Res 2000 605 19 8 Brown CD Higgins M Donato KA Rohde FC Garrison R Obarzanek E 40. Kinosian B, Glick H, Garland G. Cholesterol and coronary heart disease: predicting risks by levels and ratios. Ann Intern Med. 1994;121:641-7. Cholesterol and coronary heart disease: predicting risks by levels and ratios Ann Intern Med 1994 641 7 121 Kinosian B Glick H Garland G 41. Stampfer MJ, Sacks FM, Salvini S, Willett WC, Hennekens CH. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. N Engl J Med. 1991;325:37381. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction N Engl J Med 1991 373 81 325 Stampfer MJ Sacks FM Salvini S Willett WC Hennekens CH 42. Bersot TP, Pepin GM, Mahley RW. Risk determination of dyslipidemia in populations characterized by low levels of high-density lipoprotein cholesterol. Am Heart J. 2003;146:1052-9. Risk determination of dyslipidemia in populations characterized by low levels of high-density lipoprotein cholesterol Am Heart J 2003 1052 9 146 Bersot TP Pepin GM Mahley RW 43. Lemieux I, Lamarche B, Couillard C, Pascot A, Cantin B, Bergeron J, et al. Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study. Arch Intern Med. 2001;161:2685-92. Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study Arch Intern Med 2001 2685 92 161 Lemieux I Lamarche B Couillard C Pascot A Cantin B Bergeron J 44. Jeppesen J, Facchini FS, Reaven GM. Individuals with high total cholesterol/ HDL cholesterol ratios are insulin resistant. J Intern Med. 1998;243:293-8. Individuals with high total cholesterol/ HDL cholesterol ratios are insulin resistant J Intern Med 1998 293 8 243 Jeppesen J Facchini FS Reaven GM 45. McLaughlin T, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med. 2003;139:802-9. Use of metabolic markers to identify overweight individuals who are insulin resistant Ann Intern Med 2003 802 9 139 McLaughlin T Abbasi F Cheal K Chu J Lamendola C Reaven G 46. Rodriguez C, Calle EE, Patel AV, Tatham LM, Jacobs EJ, Thun MJ. Effect of body mass on the association between estrogen replacement therapy and mortality among elderly US women. Am J Epidemiol. 2001;153:145-52. Effect of body mass on the association between estrogen replacement therapy and mortality among elderly US women Am J Epidemiol 2001 145 52 153 Rodriguez C Calle EE Patel AV Tatham LM Jacobs EJ Thun MJ Original Articles Gender-related associations of increased body mass index with clinical and laboratory variables in individuals with no evidence of heart disease

BACKGROUND: In clinical practice, the patients we care for display a wide range of body mass indices, from lean to obese. This finding may be the sole apparent clinical abnormality. OBJECTIVE: To evaluate clinical and laboratory variables that might be associated with increased body mass index in asymptomatic men and women with no evidence of heart disease, to provide data to substantiate medical recommendations in a study sample from our everyday practice. METHODS: The subjects aged 14 to 74 years (mean 40.6 years), 295 men (43.1%) and 389 women (56.9%) The associations between body mass index stratified by gender and clinical and laboratory variables were analyzed using the Spearman correlation coefficient and multiple linear regression. RESULTS: The mean body mass index (BMI) did not differ significantly between women (26.15 Kg/m²) and men (26.33 Kg/m²). In the multiple linear regression model, the ratios of total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) (beta = 1.1320; p < 0.001) and serum glucose (beta= 0.0233; p = 0.023) were independently correlated with body mass index in women. In men, the variables independently correlated with BMI were the TC/HDL-C (beta = 0.793; p < 0.001) and age (beta = 0.0464; p = 0.030). CONCLUSION: In men and women with no evidence of heart disease, TC/HDL-C increased with body mass index in both genders. Other indices associated with BMI included serum glucose in women and age in men. Clinical and laboratory variables associated with body mass index may differ in relation to gender.

 Body mass index dyslipidemias risk factors public health

ORIGINAL ARTICLE

Gender-related associations of increased body mass index with clinical and laboratory variables in individuals with no evidence of heart disease

Fernando Araújo; Alice Tatsuko Yamada; Marcello Ricardo Paulista Markus; Ivana Antelmi; Maria do Rosário Dias de Oliveira Latorre; Alfredo José Mansur

Instituto do Coração - InCor, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP - Brazil

Mailing address

SUMMARY

BACKGROUND: In clinical practice, the patients we care for display a wide range of body mass indices, from lean to obese. This finding may be the sole apparent clinical abnormality.

OBJECTIVE: To evaluate clinical and laboratory variables that might be associated with increased body mass index in asymptomatic men and women with no evidence of heart disease, to provide data to substantiate medical recommendations in a study sample from our everyday practice.

METHODS: The subjects aged 14 to 74 years (mean 40.6 years), 295 men (43.1%) and 389 women (56.9%) The associations between body mass index stratified by gender and clinical and laboratory variables were analyzed using the Spearman correlation coefficient and multiple linear regression.

RESULTS: The mean body mass index (BMI) did not differ significantly between women (26.15 Kg/m2) and men (26.33 Kg/m2). In the multiple linear regression model, the ratios of total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) (b = 1.1320; p < 0.001) and serum glucose (b = 0.0233; p = 0.023) were independently correlated with body mass index in women. In men, the variables independently correlated with BMI were the TC/HDL-C (b = 0.793; p < 0.001) and age (b = 0.0464; p = 0.030).

CONCLUSION: In men and women with no evidence of heart disease, TC/HDL-C increased with body mass index in both genders. Other indices associated with BMI included serum glucose in women and age in men. Clinical and laboratory variables associated with body mass index may differ in relation to gender.

Key words: Body mass index; dyslipidemias/epidemiology; risk factors; public health.

Introduction

Body mass index (BMI) has been defined as weight in kilograms divided by the square of the height in meters (kg/m2) and is a surrogate measure of overweight and obesity in clinical practice and in epidemiological studies1. Overweight and obesity, evaluated by body mass index, is currently recognized as an important public health problem in several countries2,3, including Brazil4, and is associated with increased risk of cardiovascular diseases5 among men6-8 and women9-11. In previous studies, the relationship of body mass index to cardiovascular diseases demonstrated a strong and consistent association with risk factors for cardiovascular diseases, such as high blood pressure, glucose intolerance, diabetes and dyslipidemia12-14 .

In clinical practice, in addition to patients with increased risk of cardiovascular diseases, we also care for patients of low cardiovascular risk that seek cardiac health evaluation (check up) and who present a wide range of body mass indices, from lean to obese. In many of these patients, the main abnormality identified in clinical evaluation may be an increase in the body mass index. In addition to medical advice for changes in life style aimed at weight loss, it would be interesting to assess the clinical and laboratory variables associated with increased body mass index to obtain data from patients we care, in order to provide medical advice regarding cardiovascular disease prevention.

We hypothesized that certain clinical and laboratory variables regularly obtained in everyday practice might be associated with increases in body mass index, and that such an association might differ depending on gender.

The objectives of this study were to evaluate clinical and laboratory variables relative to body mass index increases and to evaluate these variables in relation to gender in a cohort of asymptomatic outpatients with no evidence of heart disease after careful clinical and laboratory examinations.

Methods

Type of study and setting - A cohort of asymptomatic individuals, with no evidence of heart disease after careful clinical and laboratory examinations, was established in a General Outpatient Clinics Unit of a tertiary care university hospital that provides also primary and secondary levels of care (cardiovascular health examination, second opinion and preoperative cardiac evaluation).

Sample and procedures - The evaluation included careful clinical examination, electrocardiogram and chest X-ray. Ethnic groups were categorized as white, black and mulatto (a person of mixed white and black ancestry). Smoking habits were assessed by questioning during clinical examination and subjects were categorized as either nonsmokers or current smokers. Asymptomatic individuals with normal clinical examination, as well as normal electrocardiogram and chest X-rays, were invited to participate in this study. Individuals who agreed to participate were submitted to further laboratory work-up, including treadmill electrocardiographic exercise stress test and two-dimensional transthoracic Doppler echocardiography.

Laboratory work-up included serum glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol), total cholesterol/HDL-cholesterol ratio, LDL-cholesterol/HDL-cholesterol ratio, triglycerides, uric acid, thyroid-stimulating hormone (TSH), creatinine and urine analysis.

Inclusion criteria - We included in the study asymptomatic Brazilian men and women older than 14 years of age and with normal clinical examination, as well as normal electrocardiogram and chest X-rays.

Exclusion criteria - We excluded individuals with past medical history of cardiovascular disease, systemic hypertension, Trypanosoma cruzi infection (Chagas' disease microorganism), diabetes mellitus, TSH < 0.05 or > 8 mg/dl, chronic obstructive pulmonary disease, asthma, renal failure, chronic inflammatory diseases, osteoarticular diseases, chronic anemia or neoplasia, and abnormal echocardiogram or electrocardiographic exercise stress test.

Study population – Six hundred and eighty - four individuals were eligible for the study. Ages ranged from 14 to 74 (mean 40.6) years, 295 (43.1%) were men and 389 (56.9%) women. Five hundred and sixteen individuals (75%) were white, 117 (17.1%) were mulatto, 32 (4.7%) were Asian and 22 (3.2%) were black.

Studied variables – We studied body mass index (kg/m2) in relation to gender, smoking status (by questioning about being nonsmokers or current smokers at the time of the clinical examination), serum glucose (mg/dl), total cholesterol (mg/dl), HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl), VLDL-cholesterol (mg/dl), total cholesterol/HDL-cholesterol ratio (TC/HDL-C), LDL-cholesterol/HDL-cholesterol ratio (LDL-C/HDL-C), triglycerides (mg/dl).

Statistical analysis – Goodness of fit for normal distribution was evaluated using the Kolmogorov-Smirnov test. Means of age, body mass index, heart rate, systolic and diastolic blood pressure, serum glucose, triglycerides and total and partial cholesterol were compared by gender using the Mann-Whitney test (as distribution of variables was not Normal). Subsequently, the analysis was further detailed to evaluate body mass index comparing men and women also in relation to smoking status. The relationship between body mass index stratified by gender and other quantitative variables was analyzed using the Spearman correlation coefficient and multiple linear regression analysis.

Variables with p < 0.20 in univariate analysis were selected to be included in multiple linear regression model. The multiple linear regression model was developed with the stepwise forward procedure. The independent variable was kept in the final model when p values were < 0.05. The multiple linear regression model that was developed for the entire sample was also applied in the analysis of each stratum. Final models for each stratum by body mass index and gender were found to be similar (data not shown). In the multiple regression model, log-transformed b results were expressedas 10b. Statistical calculations were performed with the Statistical Package for Social Science (SPSS) Statistics Set for Windows (version 10.0).

Ethical aspects - The study protocol was approved by the Human Research Ethics Committee of the Hospital and all patients signed an informed consent.

Results

Six hundred and eighty-four individuals were eligible for the study, 389 (56.9%) being women and 295 (43.1%) men. There were 285 (73%) white women and 228 white men (77%). Eighty-five (22%) women and 75 (25%) men were current smokers. In this study sample, 130 (33.6%) women and 128 (43.2%) men were overweight (BMI 25 – 29 Kg/m2) and 76 (19.4%) women and 167 (43.2%) men were obese (BMI > 30 Kg/m2).

Baseline characteristics of study participants in relation to gender revealed that there was a significant difference in mean values of serum glucose (p < 0.001), triglycerides (p < 0.001), and HDL-cholesterol (p < 0.001) between women and men. Other baseline characteristics of study participants are shown in Table 1.

Comparison of mean body mass index between women (26.15 Kg/m2) and men (26.33 Kg/m2) did not reveal a statistically significant difference. There was neither a statistically significant difference in the comparison of body mass index of women who were smokers in relation to nonsmokers, nor of men who were smokers in relation to nonsmokers (Table 2).

In women and men, univariate analysis revealed a significant correlation between body mass index and age, serum glucose, serum triglycerides and total and partial cholesterol (Table 3).

In multiple regression analysis adjusted by gender, independent variables associated with increased body mass index were identified in men: TC/HDL-C (b= 0.793; p < 0.001) and age (b= 0.0464; p = 0.030); and in women: TC/HDL-C (b= 1.1320; p < 0.001) and serum glucose (b= 0.0233; p = 0.023) (Table 4).

Discussion

In this study sample, no statistical significant difference was found in body mass index between women and men, whichis in agreement with previous studies15-17. In other report, body mass index was demonstrated to be influenced by gender18. Thus, in our practice, increased the body mass index warrants medical advice to both men and women.

Body mass index values in this study sample were within the range of lower body mass index observed in Asian19 and higher body mass index observed in european20 and american populations21. These findings may be related to differences in the characteristics of the studied populations and other demographic and clinical variables. In the outpatient sample we studied, individuals are reaching the body mass index of european and american populations.

There was no significant difference in body mass index when we compared smokers to nonsmokers either in men or in women. Smoking cessation and reduced physical activity were been demonstrated to increase the risk of gaining weight in both men and women22. In other study, sedentary lifestyle in either previous or current smokers and obesity in women were strong risk factors for poor health either as the main effect of each variable or a combined (interactions) effect23. There was no relationship between body mass index and duration of smoking cessation24. Former smokers had a larger increase in body mass index than those who had never smoked25. This is an interesting finding in our study sample that helps us to counsel patients on the relationship between smoking and body weight.

In our study, age was independently correlated with body mass index in men. In other studies, aging was demonstrated to be associated with an increase in body mass index in men26,27. Even when being overweight does not represent a serious problem in old age, obese elderly people are certainly at risk of disability, morbidity and mortality28. The increase in body mass index related to aging was suggested to be related with cardiovascular disease29. These findings suggest that gender-related factors may participate in weight gain and may warrant further studies.

Body mass index was independently correlated with serum glucose in women in this study sample. In previous studies, body mass index was positively correlated with glucose in men and women30,31. Both men and women, during 10 years of follow-up, demonstrated an increase in the incidence of diabetes together with increases in the degree of overweight32. Weight loss was effective in reducing coronary heart disease risk in insulin-resistant, obese women33,34. The results of a study that included men and women substantiate evidence to sharpen target levels for serum glucose and body mass index among patients with low HDL-C and high triglycerides35. In our study sample some unknown factors other than obesity-related well-known risk factors may be responsible for this observation.

The total cholesterol/HDL-cholesterol ratio in our study sample was independently correlated with body mass index in men and women. We did not detect an independent correlation between total cholesterol, LDL-cholesterol and HDL-cholesterol with body mass index. These findings are in agreement with previous studies among men36 and women37 and with both men and women38,39. Some studies have shown that the total cholesterol/HDL cholesterol ratio is a power ful lipoprotein marker for the development of coronary heart disease40,41, regardless of the absolute LDL-cholesterol, HDL-cholesterol42 and LDL-cholesterol/HDL-cholesterol ratio43. Patients with a high total cholesterol/HDL-cholesterol ratio were also significantly more insulin resistant44. Insulin resistance is also related to obesity45. Thus, other metabolic characteristics may be involved in the pathophysiology of the association of total cholesterol/HDL cholesterol ratio and increase in body mass index.

Our study has limitations. We screened a sample of asymptomatic patients with normal clinical examination that may not be representative of the whole population. Correlation indices of clinical and laboratory variables associated with the increase in body mass index was modest, but significant. Clinical implications of these results, specifically when we analyzed the clinical meaning of increased body mass index, must be taken into a wider context in the study of associated clinical and laboratory variables. Hormone replacement therapy may also influence body mass index46 and was not evaluated at the time the study was launched. However, hormone replacement therapy is not commonplace in the population we care for.

In conclusion, our data demonstrated that in healthy men and women showing no evidence of heart disease, total cholesterol/HDL-cholesterol ratio increased with increased body mass index in both men and women. Other indices that are associated with body mass index included serum glucose in women and age in men. Clinical interpretation of clinical and laboratory variables associated with body mass index may benefit from being more gender-specific.

References

Fernando Araújo

Rua Mozelos, 13

02073-100 - São Paulo, SP - Brazil

E-mail:

grafernando@incor.usp.br

Manuscript received February 12, 2006; revised received February 2, 2007; accepted March 3, 2007.