Prevalence of peripheral occlusive arterial disease in patients with chronic renal failure

Abstracts

Contexto: A doença arterial obstrutiva periférica tem sido reconhecida como um sensível marcador de aterosclerose sistêmica e preditora de eventos cardiovasculares. Apesar da alta prevalência da doença cardiovascular, há poucos estudos sobre a doença arterial obstrutiva periférica em pacientes com insuficiência renal crônica em tratamento hemodialítico. Objetivo: Determinar a prevalência de doença arterial obstrutiva periférica em pacientes com insuficiência renal crônica em uma clínica de referência para tratamento hemodialítico no estado de Sergipe. Métodos: Trata-se de um estudo transversal, realizado no período de junho a novembro de 2008, em uma clínica de referência para tratamento de pacientes com insuficiência renal crônica. Foram caracterizados como portadores de doença arterial obstrutiva periférica os pacientes que apresentavam índice tornozelo-braquial (ITB) ≤ 0,9. Resultados: De uma população de 239 pacientes com insuficiência renal crônica, foram avaliados 201. Destes, 28 (14%) apresentavam insuficiência arterial periférica com ITB ≤ 0,9. A idade variou de 24 a 82 anos, com média de 52 anos. A hipertensão e a dislipidemia foram os fatores de risco mais frequentes. Dos pacientes com doença arterial obstrutiva periférica, 89% eram dislipidêmicos, 71% hipertensos e 29% tinham coronariopatias. Conclusão: A prevalência de doença arterial obstrutiva periférica em doentes com insuficiência renal crônica foi de 14%.

Insuficiência renal crônica; doença arterial obstrutiva periférica; índice tornozelo-braquial

ORIGINAL ARTICLE

Prevalence of peripheral occlusive arterial disease in patients with chronic renal failure

José Aderval Aragão^I; Francisco Prado Reis^II; Roberto Ribeiro Borges Neto^III; Marina Elizabeth Cavalcanti de Sant’Anna Aragão^IV; Marco Antonio Prado Nunes^V; Vera Lúcia Corrêa Feitosa^VI

^IProfessor adjunto, Anatomia Humana, Universidade Federal de Sergipe (UFS), Aracaju, SE. Professor adjunto III, Anatomia Humana, Universidade Tiradentes (UNIT), Aracaju, SE. Doutorando, Curso de Pós-Graduação em Angiologia e Cirurgia Vascular, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP.

^IIProfessor titular, Neuroanatomia, UNIT, Aracaju, SE. Coordenador, Laboratório de Morfologia e Biologia Estrutural, Instituto de Tecnologia e Pesquisa, UNIT, Aracaju, SE

^IIIAcadêmico de Medicina, UFS, Aracaju, SE

^IVMédica, Serviço de Segurança e Medicina do Trabalho, Prefeitura Municipal de Aracaju, SE

^VProfessor assistente, Anatomia, UNIT, Aracaju, SE. Doutorando, Curso de Pós-Graduação em Angiologia e Cirurgia Vascular, UNIFESP, São Paulo, SP

^VIProfessora associada, Departamento de Morfologia, UFS, Aracaju, SE

Correspondence

Abstract

Background: Peripheral occlusive arterial disease has been found to be a sensitive marker of systemic atherosclerosis and a predictor of other cardiovascular diseases. In spite of the high prevalence of the cardiovascular diseases, there are few studies about peripheral occlusive arterial disease in patients with chronic renal failure under hemodialysis treatment.

Objective: To determine the prevalence of peripheral occlusive arterial disease in patients with chronic renal failure under hemodialysis treatment at a center of excellence in the State of Sergipe, Brazil.

Methods: A cross-sectional study was conducted from June to November 2008 at a center of excellence for the treatment of patients with chronic renal failure. Those patients with the ankle-brachial index (ABI) ≤ 0.9 were diagnosed as having peripheral occlusive arterial disease.

Results: From a population of 239 individuals with chronic renal failure, 201 were evaluated. Of that, 28 (14%) had peripheral arterial insufficiency with ABI ≤ 0.9. Their age ranged from 24 to 82 years (mean age = 52 years). Hypertension and dyslipidemia were the more frequent risk factors. Among the patients with peripheral occlusive arterial disease, 89% had dyslipidemia; 71% had high blood pressure; and 29% had coronary diseases.

Conclusion: The prevalence of peripheral occlusive arterial disease in patients with chronic renal failure was 14%.

Keywords: Chronic renal failure, peripheral occlusive arterial disease, ankle-brachial index.

Introduction

Peripheral occlusive arterial disease (POAD) is a gradual pathological process of diminished blood flow. It can be either symptomatic or asymptomatic. The disease leads to less oxygen being transported to tissues, to the point of occluding arteries in the lower limbs. The disease is a leading cause of death in the Western world^1-6.

POAD is associated with risk factors (RF) such as age, smoking, diabetes mellitus, systemic hypertension (SHT), dyslipidemia, and a sedentary lifestyle, all of which contribute to the progressive, generalized development of atherosclerotic plaques. Smoking and DM stand out among those factors, since each seems to imply a three- to fourfold increase in risk of POAD^7-10. Recently, other factors have been considered: hyperhomocysteinemia, fibrinogen, high C-reactive protein (CRP), and chronic renal failure (CRF)^11-19.

High prevalence of cardiovascular disease among CRF patients leads to mortality rates ten times as high as those found in the general population²⁰. Using the ankle-brachial index (ABI), Vinuesa et al.²¹ found 32 percent prevalence for POAD among pre-dialytic chronic renal failure patients. Using the same diagnostic method, Hiatt¹¹, Selvin & Erlinger¹² and Leibson et al.²² found prevalence ranged from 4.3 to 26 percent in the general population.

ABI is a low cost, noninvasive, easy to use method with high degrees of sensitivity and specificity. Under normal conditions, systolic pressure of the lower limbs is equal to, or slightly higher than, that of the upper limbs. When the lower limbs have arterial obstructions, systolic blood pressure at the ankle level drops, decreasing ABI values. An ABI = 0.9 has 90 to 97 percent sensitivity and 98 to 100 percent specificity for detecting arterial stenoses compromising 50 percent of the lumen of one or more high diameter vessels of the lower limbs^{9,13,18,23,24}. Considering the high rate of prevalence, high morbidity and mortality and the influence POAD can have on survival rates for CRF patients, early diagnosis of this pathological process is key.

It is estimated that POAD prevalence ranges from 15 to 20 percent among people 55 years old or more, and that around 70 to 80 percent of patients with POAD are asymptomatic⁴. However, the prevalence jumps to 30 to 38 percent in 24 percent of patients aged 40 or older who have CRF and are undergoing dialytic treatment^{11,12,22,25-27}. The objective this study was to establish POAD prevalence if CRF patients undergoing hemodialytic treatment.

Method

This is a cross-sectional study, performed from June to November 2008, at a reference clinic for hemodialytic treatment CRF patients in the state of Sergipe, Northeastern Brazil. The project was approved by the Universidade Federal de Sergipe Research Ethics Committee under protocol number 3045.0.000.107-08.

Patients were asked to take part of the study one hour before the haemodialysis session. If after reading the informed consent form they agreed to participate, they were included. Patients were excluded if they were under the age of 18, had indigenous ancestry, were pregnant, had an amputated upper or lower limb, or had a bilateral arteriovenous fistula. Information regarding age, gender, coronary disease, smoking, hypertension, haemodialysis time, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and capillary glycemia was collected using forms. Patients were considered diabetic if fasting glycemia > 126 mg/dL or if they were undergoing pharmacological treatment; to have coronary disease if they had positive past history; smoking if currently a smoker; dyslipidemic if they had high TC or low HDL-c; hypertensive if blood pressure (BP) = 140 x 90 mmHg or if using antihypertensive medication. A sphygnomanometer and a portable vascular Doppler system with 10 MHz transducer (DV 600^®, WEM Equipamentos Eletrônicos, São Paulo, Brazil) were used to measure systolic blood pressure (SBP) in the upper (brachial artery) and lower (anterior and/or posterior tibial artery) limbs. Patients were classified as having POAD if ABI = 0.9^28.29.

Results

At a reference clinic for hemodialytic treatment CRF patients in the state of Sergipe, Northeastern Brazil, 239 patients with CRF were selected for the study. Of those, 38 were then excluded: 2 because they were not 18 years old or older, three because they had amputated lower limbs, eight because of arteriovenous fistulas in the upper limbs, and 25 because they refused to participate. Patient haemodialysis time ranged from 1 to 151 months, mean average 33.72±29.72 months.

Among the 201 patients, age ranged from 18 to 86 years, mean average 47.55±14.92 years; 129 were male. There were high rates of hypertension and dyslipidemia, regardless of gender (Table 1). HDL-c levels were low for 145 (88%) dyslipidemic patients, 90 (62%) of which were male and 55 (38%) female.

Smokers, predominantly male (76%), smoked on average 19.8 cigarettes per day. Coronary disease was associated with hypertension in 75 percent of cases (30/40), and with dyslipidemia in 80 percent (32/40). Among dyslipidemic patients, 16 percent (5/32) were hypertensive and had TC > 200 mg/dL, while 84 percent (27/32) had HDL-c < 40 mg/dL for men or < 50 mg/dL for women.

POAD was found in 28 (14%) of the 201 patients, seven of which were women and 21 were men. All participants had variable levels of arterial insufficiency and ABI = 0,9. ABI was normal for 148 (74%) patients, 25 (12%) of which had ABI > 1.4.

The age of POAD patients ranged from 24 to 82 years old, mean average 52.03±17.36 years. Distribution of POAD patients by RF and by gender showed hypertension and dyslipidemia were the most common risk factors (Table 2).

Correlation between risk factors shows strong association between hypertension and coronary disease. Overall, dyslipidemia had the strongest association with other factors (Table 3). Of 25 dyslipidemic patients, five (20%) had TC > 200 mg/dL and 20 (80%) had altered HDL-c levels, < 40 mg/dL for men and < 50 mg/dL for women.

Discussion

POAD can be defined as a manifestation of atherosclerosis in the lower limbs associated with increased morbidity and mortality, limited functioning, and worse quality of life. POAD prevalence depends on diagnostic criteria; it is significantly higher when using ABI than when estimated solely on the basis of intermittent claudication. ABI, as a marker of asymptomatic POAD, provides important information about subclinical atherosclerosis, as well as being a key predictor of cardiovascular events^3,30,31.

In most epidemiological studies, POAD prevalence ranges from 3 to 10 percent, increasing circa 15 to 20 percent for patients over 70 years old³². In this study, POAD prevalence among CRF patients undergoing hemodialytic treatment was 14 percent, matching the findings of Hiatt¹¹, Selvin & Erlinger¹², Leibson et al.²², and Hasimu et al.³³, who report prevalence ranging from 4.3 to 26 percent. According to Vinuesa et al.²¹, however, the rate of POAD among pre-dialytic chronic renal failure patients is 32 percent.

The most frequent risk factors, such as old age, DM, smoking, dyslipidemia, hypertension and coronary disease, implicated in POAD, are the same reported for coronary and carotid arteriosclerosis, though the relative importance of the various factors is different for peripheral arteriosclerosis^11,12,34. Vinuesa et al.²¹ and Selvin & Erlinger¹² report old age as extremely relevant for POAD prevalence. Similar findings have been described by the NHANES sutdy, which found POAD prevalence higher than 15 percent for patients over 70 years old⁴. In this study, mean age of POAD patients was 52.03±17.36 years.

Current studies recommend research into the link between POAD patients and diabetes, since the association probably increases POAD risk by 1.5 to 4 times^25-27. Framingham claims the association to be 20 percent³⁵, while Murabito et al.¹⁴ report 68.65 percent. In this study, there is a 25 percent association between POAD and diabetes.

Hiatt⁸ reports smoking is the most important RF for POAD. In this study, 18 percent of POAD patients were smokers. Gabriel et al.³⁶ report 68.75 percent prevalence, while others^37-39 claim approximately half of all POAD patients were smokers. The latter authors also claim that the association can be twice as strong for POAD patients than for coronary artery disease (CAD) patients.

In terms of lipid profile of patients who had CRF associated with POAD, the study found a 14 percent rate of hypercholesterolemia. In studies NHANES and PARTNERS, the rates were 60 and 77 percent, respectively^4,13. HDL-c was low for 75 percent of POAD patients in our study; the same was found by Lima et al.⁴⁰ and Brandão et al.⁴¹, who report POAD patients had low HDL-c levels.

SHT is probably the most frequent cardiovascular RF among CRF patients undergoing hemodialytic treatment. Prevalence of hypertension among POAD patients was 71 percent, a finding similar to the 70 percent found by Mittal et al.⁴², but different from the 86 percent recently reported by Agarwal et al.⁴³.

Among our POAD patients, 29 percent had coronary disease, unlike the rates found by Gabriel et al.³⁶ and Sukhija et al.⁴⁴, who report rates of 90.76 and 98 percent, respectively. Hasimu et al.³³, meanwhile, report a lower rate: 25.4 percent.

Conclusion

At a reference clinic for hemodialytic treatment CRF patients in the state of Sergipe, Northeastern Brazil, POAD prevalence was 14 percent, and the most frequent RF were hypertension and dyslipidemia.

Acknowledgments

The authors would like to thank Dr. Manuel Pacheco de Andrade, for allowing this study to be performed at Clinese, and Professor Rute Santana Reis, for revising the spelling and organizing data tables.

References

• 1. Garcia LA. Epidemiology and pathophysiology of lower extremity peripheral arterial disease. J Endovasc Ther. 2006;13 Suppl 2:II3-9.
• 2. Hilleman DE. Management of peripheral arterial disease. Am J Health Syst Pharm. 1998;55(19 Suppl 1):S21-7.
• 3. Lamina C, Meisinger C, Heid IM, et al. Ankle-brachial index and peripheral arterial disease. Gesundheitswesen. 2005;67 Suppl 1:S57-61.
• 4. Norman PE, Eikelboom JW, Hankey GJ. Peripheral arterial disease: prognostic significance and prevention of atherothrombotic complications. Med J Aust. 2004;181:150-4.
• 5. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317-24.
• 6. Nunes JLB, Filho JSA, Neto AMS, et al. Doença arterial oclusiva periférica de membros inferiores em hospitais públicos de Salvador: perfil dos pacientes e do atendimento. J Vasc Bras. 2002;1:201-6.
• 7. Burns P, Lima E, Bradbury W. What constitutes best medical therapy for peripheral arterial disease? Eur J Vasc Endovasc Surg. 2002;24:6-12.
• 8. Hiatt WR. Pharmacologic therapy for peripheral arterial disease and claudication. J Vasc Surg. 2002;36:1283-91.
• 9. Ouriel K. Peripheral arterial disease. Lancet. 2001;358:1257-64.
• 10. Task Working Group. Management of Peripheral Arterial Disease (PAD) TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000;31(1 Pt 2):3-9.
• 11. Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 2001;344:1608-21.
• 12. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation. 2004;110:738-43.
• 13. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5-67.
• 14. Murabito JM, Evans JC, Nieto K, Larson MG, Levy D, Wilson PW. Prevalence and clinical correlates of peripheral arterial disease in the fragmingham offspring study. Am Heart J. 2002;143:961-5.
• 15. OHare AM, Bertenthal D, Shlipak MG, Sen S, Chren MM. Impact of renal insuffiency on mortality in advanced lower extremity peripheral arterial disease. J Am Soc Nephrol. 2005;16:514-9.
• 16. Carbayo JA, Divisón JA, Escribano J, et al. Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample. Nutr Metab Cardiovasc Dis. 2007;17:41-9.
• 17. OHare AM, Rodriguez RA, Bacchetti P. Low ankle-brachial index associated with rise in creatinine level over time: results from the atherosclerosis risk in communities study. Arch Intern Med. 2005;165:1481-5.
• 18. Wattanakit K, Folsom AR, Selvin E, et al. Risk factors for peripheral arterial disease incidence in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis. 2005;180:389-97.
• 19. Ostchega Y, Paulose-Ram R, Dillon CF, Gu Q, Hughes JP. Prevalence of peripheral arterial disease and risk factors in persons aged 60 and older: data from the National Health and Nutrition Examination Survey 1999-2004. J Am Geriatr Soc. 2007;55:583-9.
• 20. Tonelli M, Bohm C, Pandeya S, Gill J, Levin A, Kiberd BA. Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency. Am J Kidney Dis. 2001;37:484-9.
• 21. Vinuesa SG, Ortega M, Martinez P, Goicoechea M, Campdera FG, Luno J. Subclinical peripheral arterial disease in patients with chronic kidney disease: prevalence and related risk factors. Kidney Int Suppl. 2005;93:S44-7.
• 22. Leibson CL, Ransom JE, Olson W, Zimmerman BR, Ofallon WM, Palumbo PJ. Peripheral arterial disease, diabetes, and mortality. Diabetes Care. 2004;27:2843-9.
• 23. Criqui MH, Denenberg JO, Bird CE, Fronek A, Klauber MR, Langer RD. The correlation between symptoms and non-invasive test results in patients referred for peripheral arterial disease testing. Vasc Med. 1996;1:65-71.
• 24. Normas de orientação clínica para prevenção, diagnóstico e tratamento da doença arterial obstrutiva periférica (DAOP). Diagnóstico da doença arterial obstrutiva periférica (DAOP). J Vasc Bras. 2005;4(Supl.4):S222-8.
• 25. Makdisse M. Índice tornozelo-braquial: importância e uso na prática clínica. São Paulo: Segmento Farma; 2004. p. 38.
• 26. Kauffman P. Avaliação do perfil lipídico na doença arterial periférica. J Vasc Bras. 2005;4:120-1.
• 27. Carmo WB, Pinheiro HS, Bastos MG. Doença arterial obstrutiva de membros inferiores em pacientes com doença renal crônica pré-dialítica. J Bras Nefrol. 2007;29:127-34.
• 28. Lyben SP, Joseph D. The clinical presentation of peripheral arterial disease and guidance for early recognition. Cleve Clin J Med. 2006;73:S15-21.
• 29. Meru AV, Mittra S, Thyagarajan B, Chugh A. Intermittent claudication: an overview. Atherosclerosis. 2006;187:221-37.
• 30. Abul-Khoudoud O. Diagnosis and risk assessment of lower extremity peripheral arterial disease. J Endovasc Ther. 2006;13 Suppl 2:II10-8.
• 31. Cunha-Filho IT, Pereira DAG, Carvalho AMB, Garcia JP, Mortimer LM, Burni IC. Correlação entre o índice tornozelo-braço antes e após teste de deslocamento bidirecional progressivo. J Vasc Bras. 2007;6:332-8.
• 32. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg. 2007;33 Suppl 1:S1-75.
• 33. Hasimu B, Li J, Nakayama T, et al. Ankle brachial index as a marker of atherosclerosis in Chinese patients with high cardiovascular risk. Hypertens Res. 2006;29:23-8.
• 34. Durazzo AES, Sitrângulo Jr. CJ, Presti C, Silva ES, De Luccia N. Doença arterial obstrutiva periférica: que atenção temos dispensado à abordagem clínica dos pacientes. J Vasc Bras. 2005;
• 35. Bartholomew JR, Olin JW. Pathophysiology of peripheral arterial disease and risk factors for its development. Cleve Clin J Med. 2006;73 Suppl 4:S8-14.
• 36. Gabriel AS, Serafim PH, Freitas CEM, et al. Doença arterial obstrutiva periférica e índice tornozelo-braço em pacientes submetidos à angiografia coronariana. Rev Bras Cir Cardiovasc. 2007;
• 37. Fowkes FGR. Epidemiology of atherosclerotic arterial disease in the lower limbs. Eur J Vasc Surg. 1988;2:283-91.
• 38. Fowkes FG, Housley E, Riemersma RA, et al. Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. Am J Epidemiol. 1992;135:331-40.
• 39. Price JF, Mowbray PI, Lee AJ, Rumley A, Lowe GD, Fowkes FG. Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study. Eur Heart J. 1999;20:344-53.
• 40. Lima LM, Carvalho MG, Sabino AP, Mota APL, Fernandes AP, Sousa MO. Apo B/Apo A-I ratio in central and peripheral arterial diseases. Arq Bras Endocrinol Metab. 2007;51:1160-5.
• 41. Brandão AC, Trindade DM, Pinhel MA. Avaliação do perfil lipídico na doença arterial periférica. J Vasc Bras. 2005;4:129-36.
• 42. Mittal SK, Kowalski E Trenkle J, et al. Prevalence of hypertension in a hemodialysis population. Clin Nephrol. 1999;51:77-82.
• 43. Agarwal R, Nissenson AR, Batlle D, Coyne DW, Trout JR, Warnock DG. Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States. Am J Med. 2003;115:291-7.
• 44. Sukhija R, Aronow WS, Yalamanchili K, Peterson SJ, Frishman WH, Babu S. Association of ankle-brachial index with severity of angiographic coronary artery disease in patients with peripheral arterial disease and coronary artery disease. Cardiology. 2005;103:158-60.

Publication Dates

• Publication in this collection
  05 Apr 2010
• Date of issue
  Dec 2009

History

• Accepted
  03 Nov 2009
• Received
  07 Apr 2009