Performance of a clinical/proteomic panel to predict obstructive peripheral artery disease in patients with and without diabetes mellitus

Cian P McCarthy, Shreya Shrestha, Nasrien Ibrahim, Roland R J van Kimmenade, Hanna K Gaggin, Renata Mukai, Craig Magaret, Grady Barnes, Rhonda Rhyne, Joseph M Garasic, James L Januzzi, Cian P McCarthy, Shreya Shrestha, Nasrien Ibrahim, Roland R J van Kimmenade, Hanna K Gaggin, Renata Mukai, Craig Magaret, Grady Barnes, Rhonda Rhyne, Joseph M Garasic, James L Januzzi

Abstract

Background: Patients with diabetes mellitus (DM) are at substantial risk of developing peripheral artery disease (PAD). We recently developed a clinical/proteomic panel to predict obstructive PAD. In this study, we compare the accuracy of this panel for the diagnosis of PAD in patients with and without DM.

Methods and results: The HART PAD panel consists of one clinical variable (history of hypertension) and concentrations of six biomarkers (midkine, kidney injury molecule-1, interleukin-23, follicle-stimulating hormone, angiopoietin-1 and eotaxin-1). In a prospective cohort of 354 patients undergoing peripheral and/or coronary angiography, performance of this diagnostic panel to detect ≥50% stenosis in at least one peripheral vessel was assessed in patients with (n=94) and without DM (n=260). The model had an area under the receiver operating characteristic curve (AUC) of 0.85 for obstructive PAD. At optimal cut-off, the model had 84% sensitivity, 75% specificity, positive predictive value (PPV) of 84% and negative predictive value (NPV) of 75% for detection of PAD among patients with DM, similar as in those without DM. In those with DM, partitioning the model into five levels resulted in a PPV of 95% and NPV of 100% in the highest and lowest levels, respectively. Abnormal scores were associated with a shorter time to revascularisation during 4.3 years of follow-up.

Conclusion: A clinical/biomarker model can predict with high accuracy the presence of PAD among patients with DM.

Trial registration number: NCT00842868.

Keywords: claudication; peripheral vascular disease; risk factors.

Conflict of interest statement

Competing interests: JLJ has received grant support from Abbott, Cleveland Heart Labs, Singulex and Prevencio; has received consulting income from Roche Diagnostics, Critical Diagnostics and Novartis; and has participated in clinical endpoint committees/data or safety monitoring boards for Novartis, Amgen, GE, Janssen, Pfizer and Boehringer Ingelheim. CM is a consultant to Prevencio. HKG has received grant support from Roche and Portola; consulting income from Roche Diagnostics, American Regent, Amgen, Boston Heart Diagnostics and Critical Diagnostics; research payments for clinical endpoint committees for EchoSense. JMG has received consulting income from Siemens, Applied Clinical Intelligence, Bayer and Merck, Boehringer Ingelheim and AbbVie. NI has received speaker fees from Novartis. RRJvK has received grant support from Novartis. RR and GB are employees of Prevencio.

Figures

Figure 1
Figure 1
Receiver operating characteristic curve for the HART PAD score to predict obstructive peripheral arterial disease in patients with diabetes mellitus. The score had a very robust area under the receiver operating characteristic curve (AUC).
Figure 2
Figure 2
Distribution of score among patients with diabetes (positive) and without diabetes (negative) in a histogram.
Figure 3
Figure 3
Correlation between peripheral artery disease (PAD) score and mean degree of arterial stenosis in patients with and without diabetes mellitus (DM).
Figure 4
Figure 4
Kaplan-Meier survival curves depicting time to revascularisation as a function of peripheral artery disease (PAD) score. Patients in the positive group had a score greater than or equal to the optimal cut-off for the score, which was determined to be 5.607 using the optimal Youden's index (with the model’s output rescaled to the range of 0–10). Patients in the negative group had a score below 5.607. DM, diabetes mellitus.
Figure 5
Figure 5
Kaplan-Meier survival curves depicting time to revascularisation as a function of continuous HART PAD score in patients with lower extremity peripheral artery disease (PAD). Patients in the positive group had a score greater than or equal to the optimal cut-off for the score, which was determined to be 5.607 using the optimal Youden’s index (with the model’s output rescaled to the range of 0–10). Patients in the negative group had a score below 5.607. DM, diabetes mellitus.

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