AUTHOR=Li Ben , Djahanpour Niousha , Zamzam Abdelrahman , Syed Muzammil H. , Jain Shubha , Arfan Sara , Abdin Rawand , Qadura Mohammad 

TITLE=The prognostic capability of inflammatory proteins in predicting peripheral artery disease related adverse events

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1073751

DOI=10.3389/fcvm.2022.1073751

ISSN=2297-055X

ABSTRACT=Background: Levels of inflammatory proteins and their prognostic potential have been inadequately studied in peripheral artery disease (PAD) patients. In this study, we quantified and assessed the ability of inflammatory proteins in predicting adverse PAD-related events.

Methods: This was a prospective case-control study. Blood samples were collected from patients without PAD (n=202) and patients with PAD (n=275). The PAD cohort was stratified by disease severity based on ankle brachial index (ABI): mild (n=49), moderate (n=164), and severe (n=62). Patients were followed for 2 years. Plasma concentrations of 5 inflammatory proteins were measured: Alpha-2-Macroglobulin (A2M), Fetuin A, Alpha-1-Acid Glycoprotein (AGP), Serum Amyloid P component (SAP), and Adipsin. The primary outcome was major adverse limb event (MALE; composite of vascular intervention (open or endovascular) or major amputation), whereas the secondary outcome was worsening PAD status (defined as drop in ABI ≥ 0.15). Multivariable regression with adjustment for confounding variables was performed to assess the prognostic value of inflammatory proteins in predicting MALE.

Results: Relative to patients without PAD, three inflammatory proteins were differentially expressed in patients with PAD (AGP, Fetuin A, and SAP). The primary outcome (MALE) and secondary outcome (worsening PAD) status were noted in 69 (25%) and 60 (21.8%) patients, respectively. PAD-related adverse events occurred more frequently in patients with severe PAD. The most reliable predictor of the primary and secondary outcomes was the inflammatory protein AGP. On multivariable analysis, there was a significant association between AGP and MALE in all PAD disease states (mild: adjusted HR 1.13 [95% CI 1.05 – 1.47], moderate: adjusted HR 1.23 [95% CI 1.16 – 1.73], severe: adjusted HR 1.37 [95% CI 1.25 – 1.85]). High levels of AGP were associated with lower 2-year MALE-free survival in all PAD disease states (mild (64% vs. 100%, p = 0.02), moderate (64% vs. 85%, p = 0.02), severe (55% vs. 88%, p = 0.02), all PAD (62% vs. 88%, p = 0.01)).

Conclusions: Levels of inflammatory protein AGP may help in risk stratifying PAD patients at high risk of MALE and worsening PAD status and subsequently facilitate further vascular evaluation and initiation of aggressive medical management.