Diabetes is a global health crisis. The number of people with type 2 diabetes (T2D) worldwide was estimated at 425 million in 2017 and is projected to increase to 629 million by 2045.1 The increased risk for cardiovascular complications in patients with diabetes is well established, and is generally associated with an increased prevalence of known risk factors such as hypertension, dyslipidaemia and obesity.2 However, the increased risk of cardiovascular disease (CVD) in patients with T2D cannot be attributed solely to these traditional risk factors. The poor control of the majority of cardiovascular risk factors in this patient population3 suggests the need for earlier screening of at-risk patients. A variety of screening tools have been validated, but comprehensive screening is not available in many low- or middle-income countries.4 There remains a need for simple and reliable methods to identify patients with T2D who are most at risk of developing CVD.
The ankle-brachial index (ABI) is the ratio of systolic blood pressure at the ankle to that in the arm. The precise technique and calculation of the ABI have not been standardised, but the usual approach is to measure systolic pressure in both arms and at the posterior tibial and dorsalis pedis arteries in each ankle with the patient in a supine position. The ABI for each leg is then calculated as the higher pressure at the ankle divided by the higher of the left or right arm pressures.5 A number of studies have found that a low ABI is independently associated with increased risk of CVD in patients with peripheral arterial disease (PAD).6 As a result, ABI has been investigated as a predictor of CVD in other high-risk populations. In a population-based cohort study, a low ABI was found to predict an increased risk of CVD independent of the metabolic syndrome and conventional cardiovascular risk factors.7 The ABI has been recommended as one of the most feasible screening methods for CVD in patients with PAD since the equipment is inexpensive, examination takes only around 15 minutes, including a 5-minute pre-test rest in the supine position, and can be performed easily by a nurse.8
However, the accuracy of the ABI may be compromised in people with diabetes due to peripheral arterial stiffening in the ankles. Stiffening of toe arteries rarely occurs in diabetes; therefore, the toe-brachial index (TBI) appears to be a more useful measure in patients with T2D.9-12 Both manual and automatic testing techniques for measuring toe pressure are available and recommendations for their use are emerging.12 Automated systems such as the SysToe (Atys Medical, Soucieu en Jarrest, France) and MicroLife (MicroLife, Taipei, Taiwan) devices have shown high inter-rater reliability.13
There is limited research exploring the reliability of toe systolic pressures and TBIs in patients with T2D, particularly with regard to newer, more affordable devices for measuring toe pressure. A small study has established the utility of TBI in predicting recurrence of CVD in 81 patients with T2D and established ischemic heart disease.14 In another prospective study involving 200 participants with T2D and microalbuminuria, over a median follow-up of 6.1 years, reduced TBI and ABI were associated with increased risk of CVD and all-cause mortality.15
At the 20th European Congress of Endocrinology (ECE), which was held on the 19–22 May 2018 in Barcelona, Spain, a study was presented that aimed to test the predictive value of TBI as a marker for the risk of major adverse cardiovascular events (MACE) in patients with T2D.16 The study involved 741 participants in the CARDIPP epidemiological study (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care; NCT010497377). In addition to TBI, investigators measured conventional risk markers for CVD and non-invasive measurements for arterial stiffness: carotid-femoral pulse-wave velocity (PWV, with applanation-tonometry) and intima-media thickness of carotid arteries (IMT, with B-mode ultrasound). During the 7-year follow-up, 74 patients died or were hospitalised for MACE. The TBI tertiles 1 versus 3 levels were found to be negatively correlated with MACE (hazard ration [HR] for each unit of TBI 3.02, confidence interval [CI] 1.71–5.99; p<0.001). The predictive value of TBI was independent of age, sex, diabetes duration and treatment, anti-hypertensive treatment, previous CVD, glycated haemoglobin, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and mean ambulatory systolic blood pressure (HR 3.16, CI 1.50–6.70; p=0.003). Low TBI levels also predicted MACE when carotid-femoral PWV, atherosclerosis plaque identification, and IMT were added to the previous model (HR 3.12, CI 1.32–7.35; p=0.009).16
In summary, this study has added substantially to the growing body of evidence in support of the use of TBI as a predictive tool for the incidence of MACE in patients with T2D. In order to expand the role of TBI into a screening vascular test applicable to all patients with T2D, there is a need to establish cut-off values to identify high risk patients. This study was not designed to establish diagnostic cut-off values, and additional trials will be needed to validate these limits, once established. In addition, large-scale trials will be needed to establish the risk of MACE and mortality in patients with T2D for the various diagnostic limits of TBI.
Publication Date: 30 May 2018
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