, Volume 61, Issue 11, pp 2266–2276 | Cite as

Prognostic impact of the ankle–brachial index on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study

  • Claudia R. L. Cardoso
  • Juliana V. Melo
  • Guilherme C. Salles
  • Nathalie C. Leite
  • Gil F. SallesEmail author



The prognostic importance of the ankle–brachial index (ABI) in individuals with diabetes is controversial. We aimed to evaluate the relationship between the ABI and the occurrence of micro- and macrovascular complications in individuals with type 2 diabetes.


The ABI was measured at baseline in 668 individuals with type 2 diabetes, and the individuals were followed-up for a median of 10 years. Multivariate Cox analysis was used to examine associations between the ABI and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration and peripheral neuropathy) and macrovascular (total cardiovascular events, major adverse cardiovascular events [MACE] and cardiovascular mortality) complications, and all-cause mortality. The improvement in risk stratification was assessed using the C statistic and the integrated discrimination improvement (IDI) index.


During follow-up, 168 individuals had a cardiovascular event (140 MACE) and 191 individuals died (92 cardiovascular deaths); 156 individuals newly developed or experienced worsening diabetic retinopathy, 194 achieved the renal composite outcome (122 with newly developed microalbuminuria and 93 with deteriorating renal function) and 95 newly developed or experienced worsening peripheral neuropathy. The ABI, either analysed as a continuous or as a categorical variable, was significantly associated with all macrovascular and mortality outcomes, except for non-cardiovascular mortality. Individuals with a baseline ABI of ≤0.90 had a 2.1-fold increased risk of all-cause mortality (95% CI 1.3, 3.5; p = 0.004), a 2.7-fold excess risk of cardiovascular mortality (95% CI 1.4, 5.4; p = 0.004) and a 2.5-fold increased risk of MACE (95% CI 1.5, 4.4; p = 0.001). The ABI improved risk discrimination over classical risk factors, with relative IDIs ranging from 6.3% (for all-cause mortality) to 31% (for cardiovascular mortality). In addition, an ABI of ≤0.90 was associated with the development or worsening of peripheral neuropathy (2.1-fold increased risk [95% CI 1.1, 4.3]; p = 0.033), but not with retinopathy or renal outcomes.


A low ABI is associated with excess risk of adverse cardiovascular outcomes, mortality and peripheral neuropathy development or worsening, and improves cardiovascular risk stratification. The ABI should therefore be routinely evaluated in individuals with type 2 diabetes.


Ankle–brachial index Cardiovascular outcomes Microvascular complications Mortality Type 2 diabetes 



Ankle–brachial index


Cardiovascular event


Diastolic BP


Integrated discrimination improvement


Interquartile range


Major adverse cardiovascular events


Multi-Ethnic Study on Atherosclerosis


Peripheral arterial disease


Rio de Janeiro Type 2 Diabetes Cohort Study


Systolic BP


Contribution statement

CRLC, NCL and GFS conceived and designed the study, followed-up the participants and obtained the data. JVM performed the ABI measurements. CRLC drafted the manuscript. GCS and GFS analysed the data and GFS is the guarantor. All authors helped interpret the results, reviewed the manuscript and approved this version to be published. GFS had full access to all of the data and takes responsibility for the integrity of the data and the accuracy of data analysis.


This study was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) and from the Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil). The sponsors had no role in the study design, data collection or analysis, or interpretation of the results, or in the preparation, review and approval of the manuscript.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2018_4709_MOESM1_ESM.pdf (72 kb)
ESM (PDF 71 kb)


  1. 1.
    Gerhard-Herman MD, Gornik HL, Barrett C et al (2017) 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 69:e71–e126. CrossRefGoogle Scholar
  2. 2.
    O’Hare AM, Katz R, Shlipak MG, Cushman M, Newman AB (2006) Mortality and cardiovascular risk across the ankle-arm index spectrum: results from the Cardiovascular Health Study. Circulation 113:388–393. CrossRefPubMedGoogle Scholar
  3. 3.
    Ankle Brachial Index Collaboration, Fowkes FG, Murray GD, Butcher I et al (2008) Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA 300:197–208. CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Diehm C, Allenberg JR, Pittrow D, German Epidemiological Trial on Ankle Brachial Index Study Group et al (2009) Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation 120:2053–2061. CrossRefPubMedGoogle Scholar
  5. 5.
    Murphy TP, Dhangana R, Pencina MJ, D’Agostino RB Sr (2012) Ankle-brachial index and cardiovascular risk prediction: an analysis of 11,594 individuals with 10-year follow-up. Atherosclerosis 220:160–167. CrossRefPubMedGoogle Scholar
  6. 6.
    Yeboah J, Young R, McClelland RL et al (2016) Utility of nontraditional risk markers in atherosclerotic cardiovascular disease risk assessment. J Am Coll Cardiol 67:139–147. CrossRefGoogle Scholar
  7. 7.
    Lin JS, Olson CM, Johnson ES, Whitlock EP (2013) The ankle-brachial index for peripheral artery disease screening and cardiovascular disease prediction among asymptomatic adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 159:333–341. CrossRefPubMedGoogle Scholar
  8. 8.
    Alahdab F, Wang AT, Elraiyah TA et al (2015) A systematic review for the screening for peripheral arterial disease in asymptomatic patients. J Vasc Surg 61(3 Suppl):42S–53S. CrossRefPubMedGoogle Scholar
  9. 9.
    Potier L, Abi Khalil C, Mohammedi K, Roussel R (2011) Use and utility of ankle brachial index in patients with diabetes. Eur J Vasc Endovasc Surg 41:110–116. CrossRefPubMedGoogle Scholar
  10. 10.
    Aubert CE, Cluzel P, Kemel S et al (2014) Influence of peripheral vascular calcification on efficiency of screening tests for peripheral arterial occlusive disease in diabetes—a cross-sectional study. Diabet Med 31:192–199. CrossRefPubMedGoogle Scholar
  11. 11.
    Ogren M, Hedblad B, Engström G, Janzon L (2005) Prevalence and prognostic significance of asymptomatic peripheral arterial disease in 68-year-old men with diabetes. Results from the population study ‘Men born in 1914’ from Malmö, Sweden. Eur J Vasc Endovasc Surg 29:182–189. CrossRefPubMedGoogle Scholar
  12. 12.
    Mostaza JM, Manzano L, Suarez C et al (2011) Different prognostic value of silent peripheral artery disease in type 2 diabetic and non-diabetic subjects with stable cardiovascular disease. Atherosclerosis 214:191–195. CrossRefPubMedGoogle Scholar
  13. 13.
    Potier L, Roussel R, Labreuche J, REACH Investigators et al (2015) Interaction between diabetes and a high ankle-brachial index on mortality risk. Eur J Prev Cardiol 22:615–621. CrossRefGoogle Scholar
  14. 14.
    Vogt MT, McKenna M, Wolfson SK, Kuller LH (1993) The relationship between ankle brachial index, other atherosclerotic disease, diabetes, smoking and mortality in older men and women. Atherosclerosis 101:191–202. CrossRefPubMedGoogle Scholar
  15. 15.
    Leibson CL, Ransom JE, Olson W, Zimmerman BR, O’Fallon WM, Palumbo PJ (2004) Peripheral arterial disease, diabetes, and mortality. Diabetes Care 27:2843–2849. CrossRefPubMedGoogle Scholar
  16. 16.
    Hanssen NM, Huijberts MS, Schalkwijk CG, Nijpels G, Dekker JM, Stehouwer CD (2012) Associations between the ankle-brachial index and cardiovascular and all-cause mortality are similar in individuals without and with type 2 diabetes: nineteen-year follow-up of a population-based cohort study. Diabetes Care 35:1731–1735. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hendriks EJ, Westerink J, de Jong PA, SMART Study Group et al (2016) Association of high ankle brachial index with incident cardiovascular disease and mortality in a high-risk population. Arterioscler Thromb Vasc Biol 36:412–417. CrossRefPubMedGoogle Scholar
  18. 18.
    Li HY, Jiang YD, Chang TJ et al (2011) Serum vascular adhesion protein-1 predicts 10-year cardiovascular and cancer mortality in individuals with type 2 diabetes. Diabetes 60:993–999. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Gazzaruso C, Coppola A, Falcone C et al (2013) Transcutaneous oxygen tension as a potential predictor of cardiovascular events in type 2 diabetes: comparison with ankle-brachial index. Diabetes Care 36:1720–1725. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Norman PE, Davis WA, Bruce DG, Davis TM (2006) Peripheral arterial disease and risk of cardiac death in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Care 29:575–580. CrossRefPubMedGoogle Scholar
  21. 21.
    Li J, Luo Y, Xu Y et al (2007) Risk factors of peripheral arterial disease and relationship between low ankle-brachial index and mortality from all-cause and cardiovascular disease in Chinese patients with type 2 diabetes. Circ J 71:377–381. CrossRefPubMedGoogle Scholar
  22. 22.
    Bundó M, Muñoz L, Pérez C et al (2010) Asymptomatic peripheral arterial disease in type 2 diabetes patients: a 10-year follow-up study of the utility of the ankle brachial index as a prognostic marker of cardiovascular disease. Ann Vasc Surg 24:985–993. CrossRefPubMedGoogle Scholar
  23. 23.
    Abbott JD, Lombardero MS, Barsness GW et al (2012) Ankle-brachial index and cardiovascular outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. Am Heart J 164:585–590.e4. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Lau KK, Wong YK, Chan YH et al (2012) Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with type 2 diabetes. Cardiovasc Diabetol 11:101. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Mukamal KJ, Kizer JR, Djoussé L et al (2013) Prediction and classification of cardiovascular disease risk in older adults with diabetes. Diabetologia 56:275–283. CrossRefPubMedGoogle Scholar
  26. 26.
    Natsuaki C, Inoguchi T, Maeda Y et al (2014) Association of borderline ankle-brachial index with mortality and the incidence of peripheral artery disease in diabetic patients. Atherosclerosis 234:360–365. CrossRefPubMedGoogle Scholar
  27. 27.
    Yeboah J, Erbel R, Delaney JC et al (2014) Development of a new diabetes risk prediction tool for incident coronary heart disease events: the Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study. Atherosclerosis 236:411–417. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Zobel EH, von Scholten BJ, Reinhard H et al (2017) Toe-brachial index as a predictor of cardiovascular disease and all-cause mortality in people with type 2 diabetes and microalbuminuria. Diabetologia 60:1883–1891. CrossRefPubMedGoogle Scholar
  29. 29.
    American Diabetes Association (2018) 10. Microvascular complications and foot care: standards of medical care in diabetes-2018. Diabetes Care 41(Suppl 1):S105–S118. CrossRefGoogle Scholar
  30. 30.
    Hsieh MC, Tien KJ, Perng DS et al (2009) Diabetic nephropathy and risk factors for peripheral artery disease in Chinese with type 2 diabetes mellitus. Metabolism 58:504–509. CrossRefPubMedGoogle Scholar
  31. 31.
    Chen SC, Hsiao PJ, Huang JC et al (2015) Abnormally low or high ankle-brachial index is associated with proliferative diabetic retinopathy in type 2 diabetic mellitus patients. PLoS One 10:e0134718. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Yan BP, Zhang Y, Kong AP, Hong Kong JADE Study Group et al (2015) Borderline ankle-brachial index is associated with increased prevalence of micro- and macrovascular complications in type 2 diabetes: a cross-sectional analysis of 12,772 patients from the Joint Asia Diabetes Evaluation Program. Diab Vasc Dis Res 12:334–341. CrossRefPubMedGoogle Scholar
  33. 33.
    Salvotelli L, Stoico V, Perrone F et al (2015) Prevalence of neuropathy in type 2 diabetic patients and its association with other diabetes complications: the Verona Diabetic Foot Screening Program. J Diabetes Complicat 29:1066–1070. CrossRefPubMedGoogle Scholar
  34. 34.
    Cardoso CR, Leite NC, Ferreira MT, Salles GF (2015) Prognostic importance of baseline and serial glycated hemoglobin levels in high-risk patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study. Acta Diabetol 52:21–29. CrossRefPubMedGoogle Scholar
  35. 35.
    Cardoso CR, Moran CB, Marinho FS, Ferreira MT, Salles GF (2015) Increased aortic stiffness predicts future development and progression of peripheral neuropathy in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study. Diabetologia 58:2161–2168. CrossRefPubMedGoogle Scholar
  36. 36.
    Cardoso CRL, Leite NC, Dib E, Salles GF (2017) Predictors of development and progression of retinopathy in patients with type 2 diabetes: importance of blood pressure parameters. Sci Rep 7:4867.
  37. 37.
    Cardoso CRL, Leite NC, Salles GC, Ferreira MT, Salles GF (2018) Aortic stiffness and ambulatory blood pressure as predictors of diabetic kidney disease: a competing risks analysis from the Rio de Janeiro Type 2 Diabetes Cohort Study. Diabetologia 61:455–465. CrossRefPubMedGoogle Scholar
  38. 38.
    Verberk WJ, Kollias A, Stergiou GS (2012) Automated oscillometric determination of the ankle-brachial index: a systematic review and meta-analysis. Hypertens Res 35:883–891. CrossRefPubMedGoogle Scholar
  39. 39.
    Herráiz-Adillo Á, Cavero-Redondo I, Álvarez-Bueno C, Martínez-Vizcaíno V, Pozuelo-Carrascosa DP, Notario-Pacheco B (2017) The accuracy of an oscillometric ankle-brachial index in the diagnosis of lower limb peripheral arterial disease: a systematic review and meta-analysis. Int J Clin Pract 71:e12994. CrossRefGoogle Scholar
  40. 40.
    Espinola-Klein C, Rupprecht HJ, Bickel C, AtheroGene Investigators et al (2008) Different calculations of ankle-brachial index and their impact on cardiovascular risk prediction. Circulation 118:961–967. CrossRefPubMedGoogle Scholar
  41. 41.
    Wilkinson CP, Ferris FL 3rd, Klein RE, Global Diabetic Retinopathy Project Group et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110:1677–1682. CrossRefGoogle Scholar
  42. 42.
    DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845. CrossRefGoogle Scholar
  43. 43.
    Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172. CrossRefPubMedGoogle Scholar
  44. 44.
    Pencina MJ, D’Agostino RB Sr, Demler OV (2012) Novel metrics for evaluating improvement in discrimination: net reclassification and integrated discrimination improvement for normal variables and nested models. Stat Med 31:101–113. CrossRefPubMedGoogle Scholar
  45. 45.
    Pang CL, Pilkington N, Wei Y, Peters J, Roobottom C, Hyde C (2018) A methodology review on the incremental prognostic value of computed tomography biomarkers in addition to Framingham risk score in predicting cardiovascular disease: the use of association, discrimination and reclassification. BMC Cardiovasc Disord 18:39.
  46. 46.
    Barrett EJ, Liu Z, Khamaisi M et al (2017) Diabetic microvascular disease: an Endocrine Society scientific statement. J Clin Endocrinol Metab 102:4343–4410. CrossRefPubMedGoogle Scholar
  47. 47.
    Davis WA, Norman PE, Bruce DG, Davis TM (2006) Predictors, consequences and costs of diabetes-related lower extremity amputation complicating type 2 diabetes: the Fremantle Diabetes Study. Diabetologia 49:2634–2641. CrossRefPubMedGoogle Scholar
  48. 48.
    González-Clemente JM, Piniés JA, Calle-Pascual A, PADiD Study Group et al (2008) Cardiovascular risk factor management is poorer in diabetic patients with undiagnosed peripheral arterial disease than in those with known coronary heart disease or cerebrovascular disease. Results of a nationwide study in tertiary diabetes centres. Diabet Med 25:427–434. CrossRefPubMedGoogle Scholar
  49. 49.
    Mehler PS, Coll JR, Estacio R, Esler A, Schrier RW, Hiatt WR (2003) Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. Circulation 107:753–756. CrossRefPubMedGoogle Scholar
  50. 50.
    Barone Gibbs B, Dobrosielski DA, Althouse AD, Stewart KJ (2013) The effect of exercise training on ankle-brachial index in type 2 diabetes. Atherosclerosis 230:125–130. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Claudia R. L. Cardoso
    • 1
  • Juliana V. Melo
    • 2
  • Guilherme C. Salles
    • 3
  • Nathalie C. Leite
    • 1
  • Gil F. Salles
    • 1
    Email author
  1. 1.Department of Internal Medicine, School of MedicineUniversity Hospital Clementino Fraga Filho, Universidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Department of Occupational Therapy, School of MedicineUniversity Hospital Clementino Fraga Filho, Universidade Federal do Rio de JaneiroRio de JaneiroBrazil
  3. 3.Civil Engineering Program, COPPEUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

Personalised recommendations