Association of Ankle-Brachial and Toe-Brachial Indexes With Mortality in Patients With CKD.

RATIONALE & OBJECTIVE: A low ankle-brachial index (ABI) is used to diagnose peripheral artery disease (PAD) but may be normal or elevated in patients with medial arterial calcification and stiff vessels, as is common in chronic kidney disease (CKD). The toe-brachial index (TBI) has been recommended because it is not influenced by medial arterial calcification, but alone the TBI does not capture risk associated with medial arterial calcification. We hypothesized that the difference between ABI and TBI (ABI - TBI) would capture both PAD and medial arterial calcification and thus better identify mortality risk from PAD, particularly in those with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 471 patients with clinical suspicion for PAD referred for vascular testing. EXPOSURES: ABI, TBI, and ABI - TBI. OUTCOME: All-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models evaluating the association of ABI - TBI with mortality over 7 years. RESULTS: Mean age was 68 years, 89% were men, 35% had diabetes, 64% had CKD, and mean estimated glomerular filtration rate was 55 mL/min/1.73 m2. Median ABI was 0.96 (interquartile range [IQR], 0.73-1.08), median TBI was 0.62 (IQR, 0.46-0.81), and median ABI - TBI was 0.23 (IQR, 0.14-0.39). Higher ABI - TBI values were associated with increased risk in mortality only among participants with ABI values ≥ 0.9 (P = 0.03). Among participants with CKD and ABI values ≥ 0.9, participants with ABI - TBI values higher than the median had greater (HR, 1.79; 95% CI, 1.18-2.72) risk for mortality (P = 0.005). This was attenuated after age adjustment (HR, 1.41; 95% CI, 0.91-2.20) but did not change after further adjustment for confounders. LIMITATIONS: Mainly male cohort derived from a vascular laboratory; lack of limb outcomes and data for albuminuria. CONCLUSIONS: A high ABI - TBI value may be associated with higher risk for mortality in persons with CKD and a normal ABI. Age affects this association, and further studies evaluating ABI - TBI in larger populations are required.

The association of the ankle-brachial index, the toe-brachial index, and their difference, with mortality and limb outcomes in dialysis patients.

INTRODUCTION: The ankle-brachial index (ABI) is the most common test to diagnose peripheral artery disease (PAD). In dialysis patients, the ABI may under-diagnose PAD, due to a high prevalence of concomitant medial arterial calcification (MAC). The toe-brachial index (TBI) is not as susceptible to misclassification by MAC. Taking the ABI and TBI together in the form of their difference, the ABI-TBI, may provide a single measure for assessing both atherosclerosis and calcification. The relationship of these variables in dialysis patients has not been well studied. METHODS: We identified 37 dialysis patients referred for vascular studies between 2009 and 2017 in the San Diego Veterans Administration Medical Center (SDVAMC). The ABI and TBI were performed systematically for each patient, and TBI was performed regardless of ABI or waveform. We examined associations between ABI, TBI, and the difference between them (ABI-TBI) with all-cause mortality and major adverse limb events (MALE), which includes revascularizations and amputations. FINDINGS: The mean age was 65 years and 30% were African American. All patients were men, reflecting the Veterans Administration population. There were 26 deaths during follow-up and mortality was highest in patients who had low ABI and low TBI and least in those with high ABI and high TBI. Persons with TBI < 0.7 had an increased risk of all-cause mortality. The ABI-TBI, and the ABI itself, were not significantly associated with all-cause mortality although the patterns were similar. DISCUSSION: Although ABI may be an important initial risk stratification tool, the TBI may be a more informative predictor of mortality in dialysis patients. Strengths of this study include a high rate of MALE and deaths. The TBI, and the difference between ABI and TBI, should be studied further in a larger cohort of persons with advanced kidney disease.

Logistic regression models to predict solvent accessible residues using sequence- and homology-based qualitative and quantitative descriptors applied to a domain-complete X-ray structure learning set.

A working example of relative solvent accessibility (RSA) prediction for proteins is presented. Novel logistic regression models with various qualitative descriptors that include amino acid type and quantitative descriptors that include 20- and six-term sequence entropy have been built and validated. A domain-complete learning set of over 1300 proteins is used to fit initial models with various sequence homology descriptors as well as query residue qualitative descriptors. Homology descriptors are derived from BLASTp sequence alignments, whereas the RSA values are determined directly from the crystal structure. The logistic regression models are fitted using dichotomous responses indicating buried or accessible solvent, with binary classifications obtained from the RSA values. The fitted models determine binary predictions of residue solvent accessibility with accuracies comparable to other less computationally intensive methods using the standard RSA threshold criteria 20 and 25% as solvent accessible. When an additional non-homology descriptor describing Lobanov-Galzitskaya residue disorder propensity is included, incremental improvements in accuracy are achieved with 25% threshold accuracies of 76.12 and 74.79% for the Manesh-215 and CASP(8+9) test sets, respectively. Moreover, the described software and the accompanying learning and validation sets allow students and researchers to explore the utility of RSA prediction with simple, physically intuitive models in any number of related applications.