Top

Diabetologia

Published in:

01-11-2018 | Article

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

Authors: Claudia R. L. Cardoso, Juliana V. Melo, Guilherme C. Salles, Nathalie C. Leite, Gil F. Salles

Published in: Diabetologia | Issue 11/2018

Abstract

Aims/hypothesis

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.

Methods

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.

Results

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.

Conclusions/interpretation

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.

Available only for authorised users

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. https://doi.org/10.1016/j.jacc.2016.11.007 CrossRefPubMed

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. https://doi.org/10.1161/CIRCULATIONAHA.105.570903 CrossRefPubMed

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. https://doi.org/10.1001/jama.300.2.197 CrossRefPubMedCentral

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. https://doi.org/10.1161/CIRCULATIONAHA.109.865600 CrossRefPubMed

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. https://doi.org/10.1016/j.atherosclerosis.2011.10.037 CrossRefPubMed

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. https://doi.org/10.1016/j.jacc.2015.10.058 CrossRefPubMedPubMedCentral

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. https://doi.org/10.7326/0003-4819-159-5-201309030-00007 CrossRefPubMed

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. https://doi.org/10.1016/j.jvs.2014.12.008 CrossRefPubMed

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. https://doi.org/10.1016/j.ejvs.2010.09.020 CrossRefPubMed

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. https://doi.org/10.1111/dme.12309 CrossRefPubMed

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. https://doi.org/10.1016/j.ejvs.2004.11.013 CrossRefPubMed

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. https://doi.org/10.1016/j.atherosclerosis.2010.10.020 CrossRefPubMed

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. https://doi.org/10.1177/2047487314533621 CrossRefPubMed

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. https://doi.org/10.1016/0021-9150(93)90116-C CrossRefPubMed

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. https://doi.org/10.2337/diacare.27.12.2843 CrossRefPubMed

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. https://doi.org/10.2337/dc12-0178 CrossRefPubMedPubMedCentral

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. https://doi.org/10.1161/ATVBAHA.115.306657 CrossRefPubMed

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. https://doi.org/10.2337/db10-0607 CrossRefPubMedPubMedCentral

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. https://doi.org/10.2337/dc12-1401 CrossRefPubMedPubMedCentral

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. https://doi.org/10.2337/diacare.29.03.06.dc05-1567 CrossRefPubMed

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. https://doi.org/10.1253/circj.71.377 CrossRefPubMed

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. https://doi.org/10.1016/j.avsg.2010.06.001 CrossRefPubMed

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. https://doi.org/10.1016/j.ahj.2012.06.017 CrossRefPubMedPubMedCentral

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. https://doi.org/10.1186/1475-2840-11-101 CrossRefPubMedPubMedCentral

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. https://doi.org/10.1007/s00125-012-2772-1 CrossRefPubMed

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. https://doi.org/10.1016/j.atherosclerosis.2014.03.018 CrossRefPubMed

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. https://doi.org/10.1016/j.atherosclerosis.2014.07.035 CrossRefPubMedPubMedCentral

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. https://doi.org/10.1007/s00125-017-4344-x CrossRefPubMed

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. https://doi.org/10.2337/dc18-S010 CrossRef

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. https://doi.org/10.1016/j.metabol.2008.11.008 CrossRefPubMed

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. https://doi.org/10.1371/journal.pone.0134718 CrossRefPubMedPubMedCentral

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. https://doi.org/10.1177/1479164115590559 CrossRefPubMed

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. https://doi.org/10.1016/j.jdiacomp.2015.06.014 CrossRef

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. https://doi.org/10.1007/s00592-014-0592-0 CrossRefPubMed

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. https://doi.org/10.1007/s00125-015-3658-9 CrossRefPubMed

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. https://doi.org/10.1038/s41598-017-05159-6

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. https://doi.org/10.1007/s00125-017-4484-z CrossRefPubMed

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. https://doi.org/10.1038/hr.2012.83 CrossRefPubMed

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. https://doi.org/10.1111/ijcp.12994 CrossRef

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. https://doi.org/10.1161/CIRCULATIONAHA.107.763227 CrossRefPubMed

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. https://doi.org/10.1016/S0161-6420(03)00475-5 CrossRefPubMed

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. https://doi.org/10.2307/2531595 CrossRefPubMed

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. https://doi.org/10.1002/sim.2929 CrossRefPubMed

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. https://doi.org/10.1002/sim.4348 CrossRefPubMed

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. https://doi.org/10.1186/s12872-018-0777-5

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. https://doi.org/10.1210/jc.2017-01922 CrossRefPubMedPubMedCentral

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. https://doi.org/10.1007/s00125-006-0431-0 CrossRefPubMed

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. https://doi.org/10.1111/j.1464-5491.2008.02402.x CrossRefPubMed

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. https://doi.org/10.1161/01.CIR.0000049640.46039.52 CrossRefPubMed

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. https://doi.org/10.1016/j.atherosclerosis.2013.07.002 CrossRefPubMedPubMedCentral

Title: 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
Authors: Claudia R. L. Cardoso
Juliana V. Melo
Guilherme C. Salles
Nathalie C. Leite
Gil F. Salles
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 11/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4709-9

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Please log in to get access to this content

Other articles of this Issue 11/2018

Unexpected subcellular distribution of a specific isoform of the Coxsackie and adenovirus receptor, CAR-SIV, in human pancreatic beta cells

Antagonising Wnt/β-catenin signalling ameliorates lens-capsulotomy-induced retinal degeneration in a mouse model of diabetes

Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study

Effect of sitagliptin on energy metabolism and brown adipose tissue in overweight individuals with prediabetes: a randomised placebo-controlled trial

Biomarkers of islet beta cell stress and death in type 1 diabetes

Anti-angiogenic effects of the DPP-4 inhibitor linagliptin via inhibition of VEGFR signalling in the mouse model of oxygen-induced retinopathy

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page