Skip to main content
Top
Published in: Diabetologia 10/2017

01-10-2017 | Article

Toe–brachial index as a predictor of cardiovascular disease and all-cause mortality in people with type 2 diabetes and microalbuminuria

Authors: Emilie H. Zobel, Bernt Johan von Scholten, Henrik Reinhard, Frederik Persson, Tine W. Hansen, Hans-Henrik Parving, Peter K. Jacobsen, Peter Rossing

Published in: Diabetologia | Issue 10/2017

Login to get access

Abstract

Aims/hypothesis

The study aimed to evaluate toe–brachial index (TBI) and ankle–brachial index (ABI) as determinants of incident cardiovascular disease (CVD) and all-cause mortality in people with type 2 diabetes and microalbuminuria.

Methods

This was a prospective study including 200 participants. Unadjusted and adjusted (traditional risk factors and additional inclusion of N-terminal pro-brain natriuretic peptide [NT-proBNP] and coronary artery calcification) Cox regression models were performed. C statistics and relative integrated discrimination improvement (rIDI) evaluated risk prediction improvement.

Results

Median follow-up was 6.1 years; 40 CVD events and 26 deaths were recorded. Lower TBI was associated with increased risk of CVD (HR per 1 SD decrease: 1.55 [95% CI 1.38, 1.68]) and all-cause mortality (1.41 [1.22, 1.60]) unadjusted and after adjustment for traditional risk factors (CVD 1.50 [1.27, 1.65] and all-cause mortality 1.37 [1.01, 1.60]). Lower ABI was a determinant of CVD (1.49 [1.32, 1.61]) and all-cause mortality (1.37 [1.09, 1.57]) unadjusted and after adjustment for traditional risk factors (CVD 1.44 [1.23, 1.59] and all-cause mortality 1.39 [1.07, 1.60]). After additional adjustment for NT-proBNP and coronary artery calcification, lower TBI remained a determinant of CVD (p = 0.023). When TBI was added to traditional risk factors, the AUC increased significantly for CVD, by 0.063 (95% CI 0.012, 0.115) from 0.743 (p = 0.016), but not for all-cause mortality; adding ABI did not improve the AUC significantly. The rIDI for TBI was 46.7% (p < 0.001) for CVD and 46.0% (p = 0.002) for all-cause mortality; for ABI, the rIDI was 51.8% (p = 0.004) for CVD and 53.6% (p = 0.031) for all-cause mortality.

Conclusions/interpretation

Reduced TBI and ABI were associated with increased risk of CVD and all-cause mortality, independent of traditional risk factors in type 2 diabetes, and improved prognostic accuracy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Hoyer C, Sandermann J, Petersen LJ (2013) The toe-brachial index in the diagnosis of peripheral arterial disease. J Vasc Surg 58:231–238CrossRefPubMed Hoyer C, Sandermann J, Petersen LJ (2013) The toe-brachial index in the diagnosis of peripheral arterial disease. J Vasc Surg 58:231–238CrossRefPubMed
2.
go back to reference Jude EB, Eleftheriadou I, Tentolouris N (2010) Peripheral arterial disease in diabetes—a review. Diabet Med 27:4–14CrossRefPubMed Jude EB, Eleftheriadou I, Tentolouris N (2010) Peripheral arterial disease in diabetes—a review. Diabet Med 27:4–14CrossRefPubMed
3.
go back to reference Martin-Fuentes M, Herranz L, Saez-de-Ibarra L, Pallardo LF (2015) Low toe-brachial pressure index predicts increased risk of recurrent cardiovascular disease in type 2 diabetes. Diabetes Care 38:e53–e54PubMed Martin-Fuentes M, Herranz L, Saez-de-Ibarra L, Pallardo LF (2015) Low toe-brachial pressure index predicts increased risk of recurrent cardiovascular disease in type 2 diabetes. Diabetes Care 38:e53–e54PubMed
4.
go back to reference 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 35:1731–1735CrossRefPubMedPubMedCentral 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 35:1731–1735CrossRefPubMedPubMedCentral
5.
go back to reference Ankle Brachial Index C, Fowkes FG, Murray GD et al (2008) Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA 300:197–208CrossRef Ankle Brachial Index C, Fowkes FG, Murray GD et al (2008) Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA 300:197–208CrossRef
6.
go back to reference 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 29:575–580CrossRefPubMed 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 29:575–580CrossRefPubMed
7.
go back to reference Potier L, Halbron M, Bouilloud F et al (2009) Ankle-to-brachial ratio index underestimates the prevalence of peripheral occlusive disease in diabetic patients at high risk for arterial disease. Diabetes Care 32:e44CrossRefPubMed Potier L, Halbron M, Bouilloud F et al (2009) Ankle-to-brachial ratio index underestimates the prevalence of peripheral occlusive disease in diabetic patients at high risk for arterial disease. Diabetes Care 32:e44CrossRefPubMed
8.
go back to reference Emanuele MA, Buchanan BJ, Abraira C (1981) Elevated leg systolic pressures and arterial calcification in diabetic occlusive vascular disease. Diabetes Care 4:289–292CrossRefPubMed Emanuele MA, Buchanan BJ, Abraira C (1981) Elevated leg systolic pressures and arterial calcification in diabetic occlusive vascular disease. Diabetes Care 4:289–292CrossRefPubMed
9.
go back to reference Young MJ, Adams JE, Anderson GF, Boulton AJ, Cavanagh PR (1993) Medial arterial calcification in the feet of diabetic patients and matched non-diabetic control subjects. Diabetologia 36:615–621CrossRefPubMed Young MJ, Adams JE, Anderson GF, Boulton AJ, Cavanagh PR (1993) Medial arterial calcification in the feet of diabetic patients and matched non-diabetic control subjects. Diabetologia 36:615–621CrossRefPubMed
10.
go back to reference Den Ruijter HM, Peters SA, Anderson TJ et al (2012) Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA 308:796–803CrossRef Den Ruijter HM, Peters SA, Anderson TJ et al (2012) Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA 308:796–803CrossRef
11.
go back to reference Yoshida M, Mita T, Yamamoto R et al (2012) Combination of the Framingham risk score and carotid intima-media thickness improves the prediction of cardiovascular events in patients with type 2 diabetes. Diabetes Care 35:178–180CrossRefPubMed Yoshida M, Mita T, Yamamoto R et al (2012) Combination of the Framingham risk score and carotid intima-media thickness improves the prediction of cardiovascular events in patients with type 2 diabetes. Diabetes Care 35:178–180CrossRefPubMed
12.
go back to reference von Scholten BJ, Reinhard H, Hansen TW et al (2015) Additive prognostic value of plasma N-terminal pro-brain natriuretic peptide and coronary artery calcification for cardiovascular events and mortality in asymptomatic patients with type 2 diabetes. Cardiovasc Diabetol 14:59CrossRef von Scholten BJ, Reinhard H, Hansen TW et al (2015) Additive prognostic value of plasma N-terminal pro-brain natriuretic peptide and coronary artery calcification for cardiovascular events and mortality in asymptomatic patients with type 2 diabetes. Cardiovasc Diabetol 14:59CrossRef
13.
go back to reference Reinhard H, Hansen PR, Persson F et al (2011) Elevated NT-proBNP and coronary calcium score in relation to coronary artery disease in asymptomatic type 2 diabetic patients with elevated urinary albumin excretion rate. Nephrol Dial Transplant 26:3242–3249CrossRefPubMed Reinhard H, Hansen PR, Persson F et al (2011) Elevated NT-proBNP and coronary calcium score in relation to coronary artery disease in asymptomatic type 2 diabetic patients with elevated urinary albumin excretion rate. Nephrol Dial Transplant 26:3242–3249CrossRefPubMed
14.
go back to reference Gaede P, Lund-Andersen H, Parving HH, Pedersen O (2008) Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 358:580–591CrossRefPubMed Gaede P, Lund-Andersen H, Parving HH, Pedersen O (2008) Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 358:580–591CrossRefPubMed
15.
go back to reference Lassen NA, Tvedegaard E, Jeppesen FI, Nielsen PE, Bell G, Gundersen J (1972) Distal blood pressure measurement in occlusive arterial disease, strain gauge compared to xenon-133. Angiology 23:211–217CrossRefPubMed Lassen NA, Tvedegaard E, Jeppesen FI, Nielsen PE, Bell G, Gundersen J (1972) Distal blood pressure measurement in occlusive arterial disease, strain gauge compared to xenon-133. Angiology 23:211–217CrossRefPubMed
16.
go back to reference Bird CE, Criqui MH, Fronek A, Denenberg JO, Klauber MR, Langer RD (1999) Quantitative and qualitative progression of peripheral arterial disease by non-invasive testing. Vasc Med 4:15–21CrossRefPubMed Bird CE, Criqui MH, Fronek A, Denenberg JO, Klauber MR, Langer RD (1999) Quantitative and qualitative progression of peripheral arterial disease by non-invasive testing. Vasc Med 4:15–21CrossRefPubMed
17.
go back to reference Reinhard H, Wiinberg N, Hansen PR et al (2011) NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis. Cardiovasc Diabetol 10:71CrossRefPubMedPubMedCentral Reinhard H, Wiinberg N, Hansen PR et al (2011) NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis. Cardiovasc Diabetol 10:71CrossRefPubMedPubMedCentral
18.
go back to reference Tarnow L, Gall MA, Hansen BV, Hovind P, Parving HH (2006) Plasma N-terminal pro-B-type natriuretic peptide and mortality in type 2 diabetes. Diabetologia 49:2256–2262CrossRefPubMed Tarnow L, Gall MA, Hansen BV, Hovind P, Parving HH (2006) Plasma N-terminal pro-B-type natriuretic peptide and mortality in type 2 diabetes. Diabetologia 49:2256–2262CrossRefPubMed
19.
go back to reference Carter SA, Lezack JD (1971) Digital systolic pressures in the lower limb in arterial disease. Circulation 43:905–914CrossRefPubMed Carter SA, Lezack JD (1971) Digital systolic pressures in the lower limb in arterial disease. Circulation 43:905–914CrossRefPubMed
20.
go back to reference American Diabetes Association (2003) Peripheral arterial disease in people with diabetes. Diabetes Care 26:3333–3341CrossRef American Diabetes Association (2003) Peripheral arterial disease in people with diabetes. Diabetes Care 26:3333–3341CrossRef
21.
go back to reference Leng GC, Fowkes FG, Lee AJ, Dunbar J, Housley E, Ruckley CV (1996) Use of ankle brachial pressure index to predict cardiovascular events and death: a cohort study. BMJ 313:1440–1444CrossRefPubMedPubMedCentral Leng GC, Fowkes FG, Lee AJ, Dunbar J, Housley E, Ruckley CV (1996) Use of ankle brachial pressure index to predict cardiovascular events and death: a cohort study. BMJ 313:1440–1444CrossRefPubMedPubMedCentral
22.
go back to reference Pencina MJ, D’Agostino RB, Vasan RS (2010) Statistical methods for assessment of added usefulness of new biomarkers. Clin Chem Lab Med 48:1703–1711CrossRefPubMedPubMedCentral Pencina MJ, D’Agostino RB, Vasan RS (2010) Statistical methods for assessment of added usefulness of new biomarkers. Clin Chem Lab Med 48:1703–1711CrossRefPubMedPubMedCentral
23.
go back to reference Hyun S, Forbang NI, Allison MA, Denenberg JO, Criqui MH, Ix JH (2014) Ankle-brachial index, toe-brachial index, and cardiovascular mortality in persons with and without diabetes mellitus. J Vasc Surg 60:390–395CrossRefPubMedPubMedCentral Hyun S, Forbang NI, Allison MA, Denenberg JO, Criqui MH, Ix JH (2014) Ankle-brachial index, toe-brachial index, and cardiovascular mortality in persons with and without diabetes mellitus. J Vasc Surg 60:390–395CrossRefPubMedPubMedCentral
24.
go back to reference 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.e4CrossRefPubMedPubMedCentral 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.e4CrossRefPubMedPubMedCentral
25.
go back to reference Ix JH, Miller RG, Criqui MH, Orchard TJ (2012) Test characteristics of the ankle-brachial index and ankle-brachial difference for medial arterial calcification on X-ray in type 1 diabetes. J Vasc Surg 56:721–727CrossRefPubMedPubMedCentral Ix JH, Miller RG, Criqui MH, Orchard TJ (2012) Test characteristics of the ankle-brachial index and ankle-brachial difference for medial arterial calcification on X-ray in type 1 diabetes. J Vasc Surg 56:721–727CrossRefPubMedPubMedCentral
Metadata
Title
Toe–brachial index as a predictor of cardiovascular disease and all-cause mortality in people with type 2 diabetes and microalbuminuria
Authors
Emilie H. Zobel
Bernt Johan von Scholten
Henrik Reinhard
Frederik Persson
Tine W. Hansen
Hans-Henrik Parving
Peter K. Jacobsen
Peter Rossing
Publication date
01-10-2017
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 10/2017
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-017-4344-x

Other articles of this Issue 10/2017

Diabetologia 10/2017 Go to the issue

Up front

Up front

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.